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PubMed1990

Organization of geniculocortical projections in turtles: isoazimuth lamellae in the visual cortex.

The projection from the dorsal lateral geniculate complex to the visual cortex in Pseudemys and Chrysemys turtles was examined by using the anterograde transport of horseradish peroxidase (HRP) in vitro and the retrograde transport of HRP in vivo. In vitro HRP injections into the lateral forebrain bundle were used to fill geniculocortical axons anterogradely, which were then analyzed in cortical wholemount preparations. Geniculocortical axons gain access to the visual cortex along its entire rostral-caudal extent. They course in slightly curved trajectories for up to 2 mm from the lateral edge of the cortex through both the lateral (or pallial thickening) and medial parts of Desan's cortical area D2. Single axons are of fine caliber. They tend to cross each other and sometimes branch in the pallial thickening, but are generally unbranched in the medial part of D2. They bear small, fusiform varicosities at irregular intervals along their lengths. Although axons show small variations in the number of varicosities per 100 microns segment, no consistent variation in varicosity number as a function of distance could be detected. These results indicate that geniculocortical axons project to the visual cortex in an orderly pattern. The retrograde transport experiments provide some clue as to the significance of this pattern. Small, ionotophoretic injections of HRP in the visual cortex retrogradely labeled neurons in the dorsal lateral geniculate complex. Injections in the rostral visual cortex retrogradely labeled neurons in the caudal pole of the geniculate complex. Injections at progressively more caudal loci within the visual cortex labeled neurons at progressively more rostral loci within the geniculate complex. Thus, there is a representation of the rostral-caudal axis of the geniculate complex along the caudal-rostral axis of the visual cortex. Consistent with the anterograde transport experiments that showed individual geniculocortical axons coursing through both lateral and medial parts of the visual cortex, HRP injections restricted to the medial edge of the visual cortex retrogradely labeled neurons along the entire dorsal-ventral axis of the geniculate complex at the appropriate rostral-caudal position. The neurophysiological studies of Mazurskaya ('72: J. Evol. Biochem. Physiol. 8:550-555; respond to a small, moving stimulus anywhere in visual space, implying a convergence of inputs from all points in visual space somewhere along the retinogeniculocortical pathway. The experiments reported here suggest a convergence in the geniculocortical projections of information along the vertical meridians, or azimuth lines, of visual space onto neurons lying along lateral to medial transects through the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

DARPP-32, a phosphoprotein enriched in dopaminoceptive neurons bearing dopamine D1 receptors: distribution in the cerebral cortex of the newborn and adult rhesus monkey.

DARPP-32, a dopamine (DA) and cAMP-regulated phosphoprotein, is associated with dopaminoceptive neurons bearing D-1 receptors in the basal ganglia. The present study addressed the distribution of DARPP-32 in the primate cerebral cortex and its putative association with D-1 receptor laden cells in this structure. DARPP-32-like immunoreactive (LIR) neurons were examined in the cerebral cortex of 3-day-old (P3), 6-week-old (P42), and adult rhesus monkeys. In the younger cases, a large number of DARPP-32 positive neurons, with the morphological characteristics of pyramidal cells, were observed throughout the cortex, in layers V-VI, and to a lesser extent in layer II and uppermost layer III. In the parietal, insular, temporal, and occipital cortices, DARPP-32 positive neurons were arranged in a monolayer in layer Va. They were often clustered in small groups with a bundling of their dendrites. In the primary motor cortex, Betz cells were among the labeled population. In the association and somatosensory areas, the basal dendrites of DARPP-32 positive neurons and the prominent tufting of their apical dendrites in layer I contributed to an essential bilaminar pattern resembling the distribution reported for DA afferents and D-1 receptors in these areas. The prominence and widespread distribution of DARPP-32 positive neurons in layer V may be a specialization of primate cortex since such cells are found only in restricted locations in rodents. The literature on the connections of the cerebral cortex suggests that a large number of the DARPP-32 positive neurons in layer VI and perhaps even in layer Va may be corticothalamic neurons. An important developmental observation was the presence of DARPP-32-LIR neurons in the white matter. They were prominent in the neonates but could not be seen in the adult. Their location as well as their type and shape were reminiscent of interstitial neurons. In the adult monkeys, the distribution of DARPP-32-LIR neurons was more circumscribed: they were numerous in the ventral temporal gyrus and in areas related to the limbic system: caudal orbitofrontal cortex, insula, temporal pole, entorhinal, and anterior cingulate cortex. Weak labeling was detected in layer Va of the superior temporal and parietal cortex, in some prefrontal areas (10, 13, and medial 9), and in the premotor and supplementary motor cortex; in adults, unlike neonates, few DARPP-32-LIR neurons were present in the dorsolateral prefrontal cortex, the primary motor or the primary visual or prestriate cortices.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1991

Autonomic responses and efferent pathways from the insular cortex in the rat.

The anatomical distribution of autonomic, particularly cardiovascular, responses originating in the insular cortex was examined by using systematic electrical microstimulation. The localization of these responses to cell bodies in the insular cortex was demonstrated by using microinjection of the excitatory amino acid, D,L-homocysteic acid. The efferents from the cardiovascular responsive sites were traced by iontophoretic injection of the anterograde axonal tracer Phaseoleus vulgaris leucoagglutinin (PHA-L). Two distinct patterns of cardiovascular response were elicited from the insular cortex: an increase in arterial pressure accompanied by tachycardia or a decrease in arterial pressure with bradycardia. The pressor responses were obtained by stimulation of the rostral half of the posterior insular cortex while depressor sites were located in the caudal part of the posterior insular area. Both types of site were primarily located in the dysgranular and agranular insular cortex. Gastric motility changes originated from a separate but adjacent region immediately rostral to the cardiovascular responsive sites in the anterior insular cortex. Tracing of efferents with PHA-L indicated a number of differences in connectivity between the pressor and depressor sites. Pressor sites had substantially more intense connections with other limbic regions including the infralimbic cortex, the amygdala, the bed nucleus of the stria terminalis and the medial dorsal and intralaminar nuclei of the thalamus. Alternatively, the depressor region of the insular cortex more heavily innervated sensory areas of the brain including layer I of the primary somatosensory cortex, a peripheral region of the sensory relay nuclei of the thalamus and the caudal spinal trigeminal nucleus. In addition, there were topographical differences in the projection to the lateral hypothalamic area, the primary site of autonomic outflow for these responses from the insular cortex. These differences in connectivity may provide the anatomic substrate for the specific cardiovascular responses and behaviors integrated in the insular cortex.

Animals↗

PubMed1991

Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex.

The topographic and laminar organization of entorhinal projections to the dentate gyrus, hippocampus, and subicular complex was investigated in the Macaca fascicularis monkey. Injections of 3H-amino acids were placed at various positions within the entorhinal cortex and the distribution of anterogradely labeled fibers and terminals within the other fields of the hippocampal formation was determined. Injections of the retrograde tracers Fast blue, Diamidino yellow, and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were also placed into the dentate gyrus, hippocampus, and subicular complex, and the distribution of retrogradely labeled cells in the entorhinal cortex was plotted using a computer-aided digitizing system. The entorhinal cortex gave rise to projections that terminated in the subiculum, in the CA1, CA2, and CA3 fields of the hippocampus, and in the dentate gyrus. Projections to the dentate gyrus, and fields CA3 and CA2 of the hippocampus, originated preferentially in layers II and VI of the entorhinal cortex whereas projections to CA1 and to the subiculum originated mainly in layers III and V. Anterograde tracing experiments demonstrated that all regions of the entorhinal cortex project to the outer two-thirds of the molecular layer of the dentate gyrus and to much of the radial extent of the stratum lacunosum-moleculare of CA3 and CA2. While the terminal distributions of entorhinal projections to the dentate gyrus, CA3, and CA2 were not as clearly laminated as in the rat, projections from rostral levels of the entorhinal cortex preferentially innervated the outer portion of the molecular layer and stratum lacunosum-moleculare, whereas more caudal levels of the entorhinal cortex projected relatively more heavily to the deeper portions of the entorhinal terminal zones. The entorhinal projection to the CA1 field of the hippocampus and to the subiculum followed a transverse rather than radial gradient of distribution. Rostral levels of the entorhinal cortex terminated most heavily at the border of CA1 and the subiculum. More caudal levels of the entorhinal cortex projected to progressively more distal portions of the subiculum (towards the presubiculum) and more proximal portions of CA1 (towards CA2). Lateral portions of the entorhinal cortex projected to caudal levels of the recipient fields and more medial parts of the entorhinal cortex projected to progressively more rostral portions of the fields.

Animals↗

PubMed1992

The organization of the thalamocortical connections of the mediodorsal thalamic nucleus in the rat, related to the ventral forebrain-prefrontal cortex topography.

The medial and central segments of the mediodorsal nucleus of the thalamus (MD) receive afferents from the ventral forebrain, including the piriform cortex, the ventral pallidum, and the amygdaloid complex. Because MD is reciprocally interconnected with prefrontal and agranular insular cortical areas, it provides a relay of ventral forebrain activity to these cortical areas. However, there are also direct projections from the piriform cortex and the amygdala to the prefrontal and agranular insular cortices. This study addresses whether this system has a "triangular" organization, such that structures in the ventral forebrain project to interconnected areas in MD and the prefrontal/insular cortex. The thalamocortical projections of MD have been studied in experiments with injections of retrograde tracers into prefrontal or agranular insular cortical areas. In many of the same experiments, projections from the ventral forebrain to MD and to the prefrontal/insular cortex have been demonstrated with anterograde axonal tracers. The connections of the piriform cortex (PC) with MD and the prefrontal/insular cortex form an organized triangular system. The PC projections to the central and medial segments of MD and to the lateral orbital cortex (LO) and the ventral and posterior agranular insular cortices (AIv and AIp) are topographically organized, such that more caudal parts of PC tend to project more medially in MD and more caudally within the orbital/insular cortex. The central and medial portions of MD also send matching, topographically organized projections to LO, AIv and AIp, with more medial parts of MD projecting further caudally. The anterior cortical nucleus of the amygdala (COa) also projects to the dorsal part of the medial segment of MD and to its cortical targets, the medial orbital area (MO) and AIp. The projections of the basal/accessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from MD to amygdaloceptive parts of prefrontal cortex, are not as tightly organized. Amygdalothalamic afferents in MD are concentrated in the dorsal half of the medial segment. Cells in this part of the nucleus project to the amygdaloceptive prelimbic area (PL) and AIp. However, other amygdaloceptive prefrontal areas are connected to parts of MD that do not receive fibers from the amygdala. Ventral pallidal afferents are distributed to all parts of the central and medial segments of MD, overlapping with the fibers from the amygdala and piriform cortex. Fibers from other parts of the pallidum, or related areas such as the substantia nigra, pars reticulata, terminate in the lateral and ventral parts of MD, where they overlap with inputs from the superior colliculus and other brainstem structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

PubMed1995

The human entorhinal cortex: a cytoarchitectonic analysis.

The entorhinal cortex of man is in the medial aspect of the temporal lobe. As in other mammalian species, it constitutes an essential component of the hippocampal formation and the route through which the neocortex interacts with the hippocampus. The importance of knowing its architecture in detail arises from the possibility of extrapolating it to experimental findings, notably in the nonhuman primate. We have investigated the cytoarchitectonic features of the human entorhinal cortex by using as a base our previous study (D.G. Amaral, R. Insausti, and W.M. Cowan [1987] J. Comp. Neurol. 264:326-355) of the nonhuman primate entorhinal cortex. We prepared serial sections of the temporal lobe from 35 normal brains. Thionin- and myelin-stained series were made of all cases. Sections spaced 500 microns apart through the full rostrocaudal extent of the entorhinal cortex were analyzed. The human entorhinal cortex is made up of six layers, of which layer IV does not appear throughout all subfields of the entorhinal cortex. The overall appearance resembles that of the adjacent neocortex in lateral and caudal portions. In harmony with general structural principles in the nonhuman primate entorhinal cortex, our analysis supports the partitioning of the human entorhinal cortex into eight different subfields. (1) The olfactory subfield (EO), the rostralmost field, is little laminated. (2) The lateral rostral subfield (ELr), laterally located, merges with the laterally adjacent perirhinal cortex. (3) The rostral subfield (ER) is between EO and ELr, with better differentiation of layers II and III than EO. (4) The medial intermediate subfield (EMI) is located at the medial border. (5) The intermediate field (EI) is a lateral continuation of EMI; lamina dissecans (layer IV) can be best appreciated in this field. (6) The lateral caudal subfield (ELc) laterally borders on EI as a continuation of ELr. (7) The caudal subfield (EC) lies caudal to the beginning of the hippocampal fissure, with a distinctive, clear space (Vc) between layers V and VI. (8) The caudal limiting field (ECL) forms the caudal termination of the entorhinal cortex. Thus our parcellation of the entorhinal cortex in man is largely parallel to that arrived at in the monkey. This close homology provides a rational basis for the application to clinical problems of anatomical and functional information obtained in experimental work in nonhuman primates.

Adolescent↗

PubMed1995

Neuropeptide changes following excitotoxic lesion of the insular cortex in rats.

Following middle cerebral artery occlusion in Wistar rats, the immunoreactivity of neuropeptide Y increased ipsilaterally in the insular cortex and basolateral nucleus of the amygdala. In addition, the immunoreactivity of leucine-enkephalin, dynorphin, and neurotensin increased in the ipsilateral central nucleus of the amygdala. The amygdalar neurochemical changes are likely the result of damage to the insular cortex, although other cortical areas were also affected by the ischemia. To investigate whether damage to the insular cortex is essential in eliciting these changes, a localized lesion of the right or left insular cortex was produced by microinjection of D,L-homocysteic acid. Control animals received injections of vehicle into the right or left insular cortex or D,L-homocysteic acid into the right primary somatosensory cortex. Neurochemical changes were examined immunohistochemically with the peroxidase-antiperoxidase reaction 5 days after the injection. The immunoreactivity of neuropeptide Y increased locally after excitotoxic damage to the insular cortex or primary somatosensory cortex. The amygdalar neurochemical changes, including neuropeptide Y increase in the basolateral nucleus and leucine-enkephalin, dynorphin, and neurotensin increase in the central nucleus, were seen only when the ipsilateral insular cortex was lesioned. These neurochemical changes were similar to those seen 5 days after middle cerebral artery occlusion. Our findings indicate that damage to the insular cortex is essential in eliciting the neurochemical changes in the ipsilateral amygdala. In addition, the change in neuropeptide Y in the cortex appears to be a local reaction occurring irrespective of location of the lesion and glutamate receptor activation may be involved.

Amygdala↗

PubMed2000

Postnatal development of differential projections from the caudal and rostral motor cortex subregions.

The primary motor cortex of cats, monkeys, and humans has distinct rostral and caudal subregions. In the cat, projections from the caudal subregion terminate predominantly in laminae 4-6 and, from the rostral subregion, in laminae 6-8. The purpose of this study was to determine if these distinctive termination patterns are present during early postnatal development, when corticospinal axons are establishing connections with spinal neurons, or if there was postnatal refinement of the distribution of terminations. We used the anterograde tracer biotinylated dextran amine (BDA) to label selectively projections from the two subregions in immature (postnatal days 25, 35 at time of analysis) and mature animals. We compared the distribution of spinal gray matter labeling from caudal and rostral motor cortex. In immature animals, substantial bilateral terminations were present after tracer injection into either subregion. Partial axon reconstructions revealed that individual axons terminated bilaterally. The dorso-ventral laminar distribution of contralateral labeling after caudal motor cortex injections was significantly more extensive for immature than mature animals. In immature animals, most of the labeling was present in laminae 5-7 (dorsal portion). with lesser amounts in laminae 1-4 and 7 (ventral portion), 8, and 9. In mature animals, there were significant reductions in the amount of label in laminae 7-9, resulting in contraction of the labeled territory. The distribution of dorsal horn-ventral horn labeling shifted from 41% and 59% in immature animals to 77% and 23% in maturity. The distribution of contralateral labeling after rostral motor cortex injections also was different in immature and mature animals, but the changes were less extensive than for the caudal motor cortex. In immature animals, the distribution of labeling was similar to that after caudal motor cortex injections in animals of the same age. In mature animals, there was a significant reduction in the amount of labeling in laminae 1-4 and a smaller reduction in 7 (ventral)-9. The overall dorsal horn-ventral horn distribution, however, remained largely unchanged, from 40% and 60% in immature animals to 44% and 56% in maturity. In immature animals after rostral motor cortex injection, corticospinal terminations were present within the lateral motor nuclei. Thus, the distinctive spinal termination patterns of caudal and rostral motor cortex in maturity each reflected postnatal refinement of the distribution of axon terminations. It is plausible that the dorso-ventral refinement of corticospinal terminations relies on activity-dependent competition between caudal and rostral motor cortex, similar to activity-dependent refinement of the laterality of terminations. Our results, however, suggest that the developmental program for achieving corticospinal connectional specificity by the two subregions is different because there was large-scale refinement of the terminations of caudal motor cortex but only local refinement of rostral motor cortex terminations.

Age Factors↗

PubMed1994

Topographic organization of collateral projections from the basolateral amygdaloid nucleus to both the prefrontal cortex and nucleus accumbens in the rat.

The basolateral amygdaloid nucleus, a limbic/autonomic center in the basal forebrain, has been known to send projection fibers to the prelimbic and dorsal agranular insular areas in the prefrontal cortex, as well as to the nucleus accumbens. In the present study, we investigated single basolateral amygdaloid nucleus neurons sending their axons to both the prefrontal cortex and nucleus accumbens. The fluorescent retrograde double-labeling technique was employed in the rat; True Blue was injected into the prelimbic or dorsal agranular insular cortex, and Diamidino Yellow into the medial or lateral part of the nucleus accumbens. The majority of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex were located, respectively, in the rostral two-thirds or caudal two-thirds of the nucleus, while those projecting to the medial or lateral part of the nucleus accumbens were diffusely distributed in the nucleus. Almost 50% of basolateral amygdaloid nucleus neurons projecting to the prelimbic cortex sent their axon collaterals to the medial part of the nucleus accumbens. About 30-40% of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex issued their axon collaterals to the lateral part of the nucleus accumbens. The axons bifurcating to both the dorsal agranular insular cortex and lateral part of the nucleus accumbens, those bifurcating to both the prelimbic cortex and lateral part of the nucleus accumbens, or those bifurcating to both the prelimbic cortex and medial part of the nucleus accumbens arose preferentially from the rostral, middle or caudal parts of the basolateral amygdaloid nucleus, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

PubMed1998

Differences in the distribution of GABA- and GAD-immunoreactive neurons in the anterior and posterior piriform cortex of rats.

There is accumulating evidence of anterior-posterior differences in the susceptibility of the piriform cortex to seizure induction and to functional alterations in response to seizures elicited from other limbic brain regions, but the reasons for such differences along the anterior-posterior axis of the piriform cortex are not clear. In the present study, GABAergic neurons have been identified in the piriform cortex of the rat at light microscopic level by immunocytochemical localization of GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase. A monoclonal antibody to GABA and, for comparison, polyclonal antibodies to GABA and glutamic acid decarboxylase were used for this purpose. In both anterior and posterior piriform cortex, the highest number and density of GABA-immunoreactive cells was found in layer II. Lower density of GABAergic cells was found in layers I and III and the subjacent endopiriform cortex. When cells were quantified in 19 corresponding sections of the piriform cortex, covering most of anterior-posterior extension of this region, there appeared to be an increased density of GABAergic neurons in sections near to or within the transition zone between anterior and posterior piriform cortex. A more detailed analysis at 4 section levels in the anterior and posterior piriform cortex and the transition zone between the 2 parts substantiated a significantly higher density of GABAergic neurons in the transition zone, which was predominantly due to increased numbers of cells in layers II and III. We propose that the transition zone between anterior and posterior piriform cortex is a location where numerous GABAergic interneurons regulate the activity of neighbouring deep pyramidal cells which receive dense excitatory input from both the olfactory bulb and distant pyramidal cells in the more anterior and posterior parts of the piriform cortex at the same time, thus increasing the risk of paroxysmal activation within this restricted area. This proposal is in line with recent observations of increased susceptibility to epileptiform activation and to kindling-induced neurochemical alterations within the transition zone between anterior and posterior piriform cortex.

Animals↗

PubMed1999

Associational projections of the anterior midline cortex in the rat: intracingulate and retrosplenial connections.

Past studies indicate that distinct areas of anterior midline cortex in the rat contribute to diverse functions, such as autonomic nervous system regulation and learning, but the anatomical substrate for these functions has not been fully elucidated. The present study characterizes the associational connections within the midline cortex of the rat by using the anterograde transport of Phaseolus vulgaris leucoagglutinin and Fluororuby. The prelimbic area and the rostral part of the anterior cingulate area (both dorsal and ventral subdivisions) are extensively interconnected with each other. In addition, the caudal half of anterior cingulate cortex has extensive projections to precentral medial cortex and caudally directed projections to retrosplenial cortex. Other cortical areas within anterior midline cortex have relatively limited cortical-cortical projections. The infralimbic, dorsal peduncular, and medial precentral cortices have dense intrinsic projections, but have either very limited or no projections to other areas in the anterior midline cortex. Although it has been suggested that cortical-cortical projections from anterior cingulate cortex and prelimbic cortex to infralimbic cortex may be important for linking learning processes with an autonomic nervous system response, the paucity of direct projections between these areas calls this hypothesis into question. Conversely, the results suggest that the anterior midline cortex contains two regions that are functionally and connectionally distinct.

Animals↗

PubMed1997

Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam.

Acute stress has been associated with activation of glutamate efflux in forebrain structures. The present study sought to characterize the extracellular dynamics of glutamate in response to acute and repeated stress in the prefrontal cortex and hippocampus in rats. One-minute sampling of extracellular glutamate levels was performed during repeated tail-pinch stress. Animals were stressed three times, beginning at approximately 10.30 a.m. and continuing at 2.5-h intervals. In the prefrontal cortex, the initial 10-min tail pinch produced a robust increase in extracellular levels of glutamate. This increase was apparent immediately (i.e. 1 min) after the start of the stress procedure. The second tail pinch produced a smaller increase in glutamate levels while the third tail pinch did not significantly increase these levels. In the hippocampus, the initial stress response was smaller in magnitude than that observed in the prefrontal cortex. Furthermore, responses to subsequent tail pinches were similar to that seen following the first tail pinch. Treatment with diazepam (3 mg/kg/i.p.) 30 min before the first stress session abolished the stress response in the prefrontal cortex and hippocampus. However, in the prefrontal cortex, the second tail pinch (performed approximately 3 h after diazepam administration) produced a robust increase in glutamate efflux. In contrast, in the hippocampus of diazepam-treated rats, the second tail pinch produced a small delayed response. Pretreatment with saline resulted in non-significant responses to all three tail pinches in the prefrontal cortex. The present study suggests that: (i) stress produces a rapid increase in glutamate efflux in the prefrontal cortex and hippocampus, (ii) repeated stress reveals tolerance in the glutamatergic response in the prefrontal cortex, (iii) saline and diazepam pretreatment reduce the stress-induced efflux of glutamate in the prefrontal cortex, and (iv) exposure to diazepam may prevent the prefrontal cortex from adapting its response to the subsequent stressor. These finding are consistent with the role of the prefrontal cortex as a region which may regulate reactions to aversive stimuli.

Animals↗

PubMed1999

Expression of cocaine sensitization: regulation by the medial prefrontal cortex.

Extracellular levels of dopamine are increased in response to systemic administration of cocaine in several brain areas including the nucleus accumbens and medial prefrontal cortex. While the cocaine-induced increase in extracellular dopamine levels in the nucleus accumbens is augmented after repeated daily cocaine, the response of extracellular dopamine levels in the medial prefrontal cortex is attenuated. Since dopamine in the medial prefrontal cortex has an inhibitory effect on nucleus accumbens dopamine levels and locomotor activity, the role of medial prefrontal cortex dopamine tolerance in the expression of sensitized locomotor behavior was further examined by injection of D-amphetamine sulfate into the prelimbic portion of the medial prefrontal cortex just prior to cocaine challenge in cocaine-sensitized rats. Male Sprague-Dawley rats were non-handled (naive) or injected with either saline (1 ml/kg, i.p.) or cocaine (15 mg/kg, i.p.) for five consecutive days. After a seven to 12 day withdrawal period, rats were microinjected with either saline or various doses of amphetamine into primarily the prelimbic region of the medial prefrontal cortex followed by systemic injection of saline or cocaine. In naive rats, intramedial prefrontal cortex amphetamine produced a trend toward decreased locomotor responding to cocaine challenge while no effect of amphetamine was evident in daily saline pretreated rats. Daily cocaine pretreated rats that received saline in the medial prefrontal cortex demonstrated a sensitized locomotor response compared to their daily saline pretreated counterparts. This sensitization was blocked by a low dose of amphetamine (0.175 microg/side) in the medial prefrontal cortex, an effect which disappeared in animals administered higher amphetamine doses. The results suggest that in rats sensitized to cocaine, decreased medial prefrontal cortex dopamine levels in response to cocaine challenge may contribute to behavioral sensitization. Furthermore, the data indicate the possibility that there is an optimal range at which medial prefrontal cortex amphetamine exerts maximal behavioral inhibition. These findings implicate a role for decreased cortical control in producing sensitized behavioral responding to cocaine.

Animals↗

PubMed1999

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment.

The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+/-1 degrees C) and dissociated slowly. The association and dissociation rate constants were 4.31+/-0.34x10(8) M(-1) x min(-1) and 1.55+/-0.38x10(-3) min(-1) respectively. Thus, the kinetic dissociation constant was 3.46+/-0.59 pM. Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding affinities (pK(D)) of [33P]-human gene 2 relaxin (B33) were 8.92+/-0.09 in atrial myocardium and 8.79+/-0.04 in cerebral cortex of male rats, and 8.79+/-0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in non-reproductive tissues. In male rats, treatment with 17beta-oestradiol (20 microg in 0.1 ml sesame oil s.c., 18-24 h) significantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no significant effect in atria and cerebral cortex, but it significantly increased the density of relaxin receptors in uterine myometrium. Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+/-0.02), and cerebral cortex (8.90+/-0.03) and uterine myometrium (8.89+/-0.03) with affinities not significantly different from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with affinities (8.35+/-0.09 in atria, 8.22+/-0.07 in cerebral cortex and 8.48+/-0.06 in uterine myometrium) significantly less than human gene 2 (B33) and porcine relaxins. Quantitative receptor autoradiography is the method of choice for measurement of affinities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17beta-oestradiol treatment produced complex effects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no effect on the atria and cerebral cortex of the female rats.

Animals↗

PubMed1998

Temporary interference in human lateral premotor cortex suggests dominance for the selection of movements. A study using transcranial magnetic stimulation.

It is known that damage to the left hemisphere can lead to movement deficits, and that patients with apraxia have difficulty in selecting movements. Neurophysiological recording studies and lesion studies have shown that the premotor cortex is important for the selection of movements in monkeys. In this study we used transcranial magnetic stimulation (TMS) to disrupt the processing in human premotor cortex. We applied TMS to normal healthy volunteers over the premotor and primary motor areas while they carried out choice reaction time and simple reaction-time tasks. We measured response times of either hand as subjects were stimulated over the left and right hemisphere separately. We found that we were able to delay responses by stimulating at short cue-stimulus intervals (100-140 ms) over premotor cortex and at longer cue-stimulus intervals (300-340 ms) over primary motor cortex while subjects performed the choice reaction-time task with the contralateral hand. We were also able to delay responses with the ipsilateral hand while stimulating over the left premotor cortex, but not while stimulating over the right premotor cortex or either sensorimotor cortex. Premotor cortex stimulation alone disrupts an early stage of movement selection; motor cortex stimulation disrupts the movements at a later stage of execution. There was no distinguishing short cue-stimulus interval effect when premotor cortex was stimulated in the simple reaction time paradigm, where the movement selection demands of the task are kept to a minimum. We conclude that the premotor cortex is important for selecting movements after a visual cue and that the left hemisphere is dominant for the rapid selection of action.

Analysis of Variance↗

PubMed1985

Comparison of proteins involved with cyclic AMP metabolism between synaptic membrane and postsynaptic density preparations isolated from canine cerebral cortex and cerebellum.

Synaptic membrane and postsynaptic density (PSD) fractions isolated from canine cerebral cortex and cerebellum were assayed for the following proteins: adenylate cyclase and phosphodiesterase (PDE) activities against cyclic AMP and cyclic GMP, the regulatory subunit of the cyclic AMP-dependent protein kinase, and the substrate proteins for this kinase. The results were expressed on the basis of both the protein content of the fractions and the number of synapses in the synaptic membrane fractions. The number of synapses on a constant protein content basis was about three times higher in the cerebral cortex synaptic membrane fraction than in the comparable cerebellar fraction. Adenylate cyclase activity was from 3.4 to 5.6 times higher in the cerebral cortex membrane fraction than in the cerebellar membrane fraction based on protein content but only slightly higher based on synapse counts. PSD fractions had no adenylate cyclase activity. The cyclic AMP-PDE activity was from 17 to 27 times higher in the cerebral cortex membrane fraction than in the cerebellar membrane fraction based on protein content, and about five times higher based on synapse counts. By doing PDE histochemistry at the electron microscopy level it was found that all the cerebral cortex PSDs in the isolated fraction contained PDE activity, none being found associated with the broken-up material in the fraction. The amount of the regulatory subunit of the cyclic AMP-dependent protein kinase was about equal in the two fractions based on protein, but about one-third lower in cerebral cortex fraction than in cerebellar fractions. In the cerebral cortex membrane fraction the primary substrate for the cyclic AMP-dependent protein kinase is synapsin I, with much lower amounts in the cerebellar membrane fraction. The PSD fraction from the two sources also showed these differences in synapsin I content. In the cerebellar membrane fraction, the primary substrate for the enzyme is a approximately 245,000 Mr protein not found in the cerebral cortex membrane fraction. The findings that the turnover of cyclic AMP is much higher in cerebral cortex synapses than in cerebellar synapses, and that differences are found between the cerebral cortex and cerebellum with regard to the substrate proteins for the cyclic AMP-dependent protein kinase indicate a divergence in the effect of cyclic AMP between cerebral cortex and cerebellar synapses.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1990

Neurotensin regulation of endogenous acetylcholine release from rat cerebral cortex: effect of quinolinic acid lesions of the basal forebrain.

The effects of neurotensin (NT) on endogenous acetylcholine (ACh) release from basal forebrain, frontal cortex, and parietal cortex slices were tested. The results show that NT differentially regulates evoked ACh release from frontal and parietal cortex slices without altering either spontaneous or evoked ACh release from basal forebrain slices. In the frontal cortex, NT significantly inhibited evoked ACh release by a tetrodotoxin (TTX)-insensitive mechanism, suggesting an action directly on cholinergic terminals. In the parietal cortex, NT enhanced evoked ACh release by a TTX-sensitive mechanism, suggesting an action of NT on the cholinergic neuron or in close proximity to the cholinergic neuron. The effects of NT on ACh release were confined to evoked ACh release; that is, spontaneous ACh release was not affected. NT did not affect spontaneous or potassium-evoked ACh release from occipital cortex slices. The second set of experiments tested the effects of quinolinic acid (QUIN) lesions of the basal forebrain cell bodies on the NT-induced regulation of evoked ACh release in the cerebral cortex. QUIN lesions of basal forebrain cell bodies caused decreases in choline acetyltransferase activity (27 and 28%), spontaneous ACh release (14 and 21%), and evoked ACh release (38 and 44%) in frontal and parietal cortex, respectively. In addition, 11 days following QUIN lesions of basal forebrain cell bodies, the action of NT to regulate evoked ACh release in frontal cortex or parietal cortex was no longer observed. The results suggest that in the rat frontal and parietal cortex, NT differentially regulates the activity of cholinergic neurons by decreasing and increasing evoked ACh release, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed2004

Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.

Adult↗