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PubMed1988

Organization of cortical and subcortical projections to medial prefrontal cortex in the cat.

We have analyzed the cortical and subcortical afferent connections of the medial prefrontal cortex (MPF) in the cat with the specific aim of characterizing subregional variations of afferent connectivity. Thirteen tracer deposits were placed at restricted loci within a cortical district extending from the proreal to the subgenual gyrus. The distribution throughout the forebrain of retrogradely labeled neurons was then analyzed. Within the thalamus, retrogradely labeled neurons were most numerous in the mediodorsal nucleus and in the ventral complex. The projection from each region exhibited continuous topography such that more medial thalamic neurons were labeled by tracer from more ventral and posterior cortical deposits. Marked retrograde labeling without any sign of topographic order occurred in a narrow medioventral sector of the lateroposterior nucleus. Several additional thalamic nuclei contained small numbers of labeled neurons. In a subset of nuclei closely affiliated with the limbic system (the parataenial, paraventricular, reuniens, and basal ventromedial nuclei), retrograde labeling occurred exclusively after deposits at extremely ventral and posterior cortical sites. Within the amygdala, retrogradely labeled neurons occupied the anterior basomedial nucleus, the posterior basolateral nucleus, and a narrow strip of the lateral nucleus immediately adjoining the basolateral nucleus. The number of labeled neurons was greater after more ventral deposits. Very ventral deposits resulted in extensive labeling of the cortical amygdala. Within the cerebral cortex, the distribution of labeled neurons depended on the location of the tracer deposit. Comparatively dorsal deposits produced prominent retrograde transport to the anterior and posterior cingulate areas, to the agranular insula, and to lateral prefrontal cortex. Comparatively ventral deposits gave rise to prominent labeling of the hippocampal subiculum, various parahippocampal areas, and prepiriform cortex. On the basis of afferent connections, it is possible to divide the cat's medial prefrontal cortex into an infralimbic component, MPFil, marked by strong afferents from prepiriform cortex and the cortical amygdala, and a dorsal component, MPFd, without afferents from these structures. Further, within MPFd, it is possible to define an axis, running from ventral and posterior to dorsal and anterior levels, along which limbic afferents gradually become weaker and projections from cortical association areas gradually become stronger.

Acetylcholinesterase↗

PubMed1988

Catalepsy after microinjection of haloperidol into the rat medial prefrontal cortex.

To investigate the behavioural role of mesocortical dopamine innervation we performed bilateral microinjections of haloperidol into various parts of the rat frontal cortex and into adjacent subcortical forebrain structures. Haloperidol (2.5 micrograms/0.5 microliter) locally injected into the medial prefrontal cortex or into the rostral part of the neostriatum resulted in the development of catalepsy as measured in the bar test. In contrast, injections of haloperidol into the nucleus accumbens, more caudal parts of the neostriatum, anterior cingulate cortex, rostral and lateral parts of the prefrontal cortex and into the lateral ventricles failed to induce catalepsy. It is concluded that blockade of dopamine receptors located in the rostral neostriatum and in the medial prefrontal cortex contributes to the development of haloperidol induced catalepsy.

Animals↗

PubMed1990

Differential effects of forced locomotion, tail-pinch, immobilization, and methyl-beta-carboline carboxylate on extracellular 3,4-dihydroxyphenylacetic acid levels in the rat striatum, nucleus accumbens, and prefrontal cortex: an in vivo voltammetric study.

In vivo voltammetry with carbon fiber electrodes was used to assess extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) levels in striatum, nucleus accumbens, and anteromedial prefrontal cortex of freely moving rats subjected to altered motor activity or anxiogenic stimuli. Forced locomotion on a rotarod for 40 min caused an increase in extracellular DOPAC levels in the striatum and to a lesser extent in the nucleus accumbens but not in the prefrontal cortex. Subcutaneous injection of the anxiogenic agent methyl-beta-carboline carboxylate (10 mg/kg) increased extracellular DOPAC levels to a similar extent in prefrontal cortex and nucleus accumbens. Immobilization for 4 min augmented dopamine (DA) metabolism preferentially in the nucleus accumbens and to a lesser extent in the prefrontal cortex. Tail-pinch caused a selective activation of DA metabolism in the nucleus accumbens. None of these stimuli altered extracellular striatal DOPAC levels. These results confirm the involvement of dopaminergic systems projecting to the striatum and nucleus accumbens in motor function and suggest that mesolimbic and mesocortical dopaminergic systems can be specifically activated by certain kinds of anxiogenic stimuli; the relative activation of either of these latter systems could depend primarily on the nature (sensory modality, intensity) of the acute stressor.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Hemispheric asymmetry in neglect produced by unilateral lesions of dorsomedial prefrontal cortex in rats.

Unilateral lesions of the medial precentral prefrontal cortex produce severe polymodal neglect which reaches a stable level of recovery over 3 to 4 weeks. Previous research has indicated that neglect is produced by unilateral destruction of this region in either hemisphere, but that the nature of the neglect produced is dependent on the hemisphere damaged. The present study is a further examination of behavioral laterality produced by this unilateral destruction. The results indicated that destruction of medial precentral cortex in the left hemisphere (n = 12) produced severe contralateral multimodal neglect of visual, somatosensory, and auditory stimuli. Identical destruction in the right hemisphere (n = 18) also produced severe neglect, but unlike the left hemisphere operates which always demonstrated contralateral neglect, there were two distinct populations of right hemisphere operates. These subjects demonstrated either ipsilateral neglect or a "switching" response pattern characterized by the initial demonstration of contralateral or ipsilateral neglect and then, during the course of recovery, severe neglect on the opposite body side. Histological analysis indicated that the left and right hemisphere lesions were equivalent, as were the lesions in the two behavioral subcategories of right hemisphere operates. Operated controls (n = 12) did not demonstrate long-standing neglect or this switching pattern. The behavioral laterality observed following unilateral destruction of medial precentral prefrontal cortex is discussed in relationship to the anatomical and neurochemical asymmetries which have been demonstrated in this cortical region.

Acoustic Stimulation↗

PubMed1991

Prefrontal cortex alpha 2 adrenoceptors and energy balance.

The sulcal prefrontal cortex (SPC) influences thermogenesis, energy substrate utilization and feeding behaviour. The present study examined the role of SPC alpha noradrenergic receptors in these effects. Fifty nmol norepinephrine (NE) injected into the SPC produced a large and long-lasting increase in respiratory quotient (RQ), indicating enhanced carbohydrate utilization and fat synthesis. This dose also reduced energy expenditure without corresponding decreases in locomotor activity, suggesting an inhibition of thermogenesis. Neither a lower dose of NE (25 nmol) injected into the SPC, nor injections of NE (50 nmol) into a variety of sites adjacent to the SPC affected energy balance. The alpha 2 agonist clonidine (20 nmol) injected into the SPC produced similar effects to 50 nmol NE, with a large increase in RQ and a decrease in thermogenesis. Forty nmol clonidine, however, decreased RQ and reduced both energy expenditure and activity. The alpha 1 agonist L-phenylephrine (20 and 40 nmol) injected into the SPC had no clear effect on energy balance. Finally, it was shown that clonidine or NE injected into the SPC promotes food intake. These results implicate alpha 2 adrenoceptors in the sulcal prefrontal cortex in the control of food intake, thermogenesis and metabolic substrate utilization.

Animals↗

PubMed1978

Subcortical afferents to the prefrontal cortex in rabbits.

The origins of cells projecting to the prefrontal cortex of the rabbit were studied, using horseradish peroxidase (HRP) technique. HRP injected into the prefrontal cortex labeled cells in the basal forebrain, lateral hypothalamus, raphe nuclei and locus coeruleus area on both sides. Labeled cells appeared also in the nucleus medialis dorsalis of the thalamus and other thalamic nuclei on the injection side.

Afferent Pathways↗

PubMed1986

Neurotransmitters, pathways and circuits as the neural substrates of self-stimulation of the prefrontal cortex: facts and speculations.

Through a multidisciplinary approach considerable progress has been made in understanding the neural substrates of self-stimulation (SS) of the medial prefrontal cortex (MPC). Thus, neuroanatomical studies have revealed that intrinsic neurones in the MPC seem to be the central elements responsible for initiating and maintaining this phenomenon in this area of the brain. Complementary to this central finding are the electrophysiological and neurohistological data reviewed here, showing that neurones in the MPC are directly activated and have monosynaptic feed-back connections with neurones located in areas which also support SS. These findings have given rise to the hypothesis that several single feed-back pathways or single circuits exist between points of SS in the MPC and points of SS in other areas of the brain. This hypothesis implies that SS in a particular area would depend not only on the intrinsic local activity induced by the electrical stimulation but on the functional and specific activity of other nuclei in the brain. The fact that lesions of single circuits, which are apparently involved in SS of the MPC such as the medial prefrontal cortex-ventrotegmental area-medial prefrontal cortex and medial prefrontal cortex-n. dorsomedialis of the thalamus-medial prefrontal cortex, do not produce a permanent decrease of SS, together with the finding that transynaptic connections seem to exist between MPC and other areas of the brain, suggests further that a complex rather than several single independent circuits could be at the neural basis of SS of the MPC. If that were the case, then SS of the MPC would not only depend upon local and single feed-back activity but upon specific functional feed-back activity among the nuclei, which in turn have single feed-back connections with the MPC (see the concept of 'complex circuit' outlined in the section of Behavioural studies). On the basis of this hypothesis no permanent changes should be expected after lesions of single pathways since physiological and even anatomical compensation could be reached through the rest of the undamaged circuit. That terminals containing specific neurotransmitters exist in layers of the PC where electrodes for SS are located has been reviewed in this paper. Some of these neurotransmitters have been suggested to be part of the local substrates activated by SS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

An excitant amino acid projection from the medial prefrontal cortex to the anterior part of nucleus accumbens in the rat.

High-affinity uptake of neurotransmitter substrates in synaptosome-containing homogenates and tissue concentrations of amino acids were examined in subcortical areas 5-6 days after bilateral N-methyl-D-aspartate lesions confined to rat medial prefrontal cortex. D-[3H]Aspartate (32% of control) and [3H] gamma-aminobutyric acid ( [3H]GABA) (60% of control) uptakes were significantly reduced in medial prefrontal cortex, whereas [3H]choline (110% of control) uptake was unchanged, suggesting the production of axon-sparing lesions. The uptake of D-[3H]aspartate (76% of control), but not of [3H]GABA or [3H]choline, was significantly reduced in nucleus accumbens, with no concomitant reduction in amino acid concentrations. When examined in serial coronal sections, reduced D-[3H]aspartate uptake was confined to the most anterior 500 micron of nucleus accumbens (67% of contralateral sample). No significant reductions of uptake or amino acid concentrations were observed in caudate putamen or ventral tegmental area. These results suggest a role for glutamate or aspartate as neurotransmitters in projections from medial prefrontal cortex to anterior nucleus accumbens. Medial prefrontal cortex may represent the major excitatory cortical input to the nucleus accumbens.

Amino Acids↗

PubMed1984

Homovanillic acid in rat caudate and prefrontal cortex following phencyclidine and amphetamine.

Phencyclidine (PCP) and d-amphetamine (AMP) had different effects upon homovanillic acid (HVA) levels in rat prefrontal cortex as compared to caudate. Lower doses of PCP increased HVA in prefrontal cortex only while lower doses of AMP decreased HVA in caudate alone. Higher doses of both drugs produced a decreased HVA in caudate and an increase in prefrontal cortex. At some doses PCP may selectively activate mesocortical dopaminergic neurons.

Animals↗

PubMed1989

Stimulation in prefrontal cortex area inhibits cardiovascular and motor components of the defence reaction in rats.

In the present investigation it was shown that electrical or chemical (D,L-homocysteic acid, DLH) stimulation in a defined area of the medial prefrontal cortex inhibits cardiovascular components of the defence reaction elicited by stimulation in the basal nucleus of the amygdala or in the hypothalamus in rats anaesthetized by Saffan. Electrical stimulation in the dorsal part of the nucleus accumbens or ventral part of the nucleus caudate had the same effect, while chemical stimulation (DLH) in these areas was not effective. In unanaesthetized rats stimulation in the prefrontal cortex or the nucleus accumbens inhibited cardiovascular and motor components of the defence reaction induced from the amygdala or hypothalamus. Stimulation in the described areas of the medial prefrontal cortex or nucleus accumbens does not induce general inhibition of motor activity since it did not affect operant, appetitive bar pressing. It is therefore concluded that the inhibition is selectively addressed to the motor activities associated with the defence reaction. It is suggested that inhibition of the cardiovascular components of the defence reaction must occur below hypothalamic level. The inhibition is most likely presynaptic since stimulation in the prefrontal cortex or nucleus accumbens alone did not produce any cardiovascular changes. It is unlikely that the efferent pathway originating in the prefrontal inhibitory area relays in the nucleus accumbens since microinjection of DLH into this nucleus was ineffective. Stimulation in "sympatho-inhibitory' areas (anterior hypothalamus, anterior cingulum) or in the nucleus raphe obscurus had no inhibitory effect on the cardiovascular components of the defence reaction.

Animals↗

PubMed1987

Anatomical and electrophysiological evidence for a direct projection from Ammon's horn to the medial prefrontal cortex in the rat.

Following microinjection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the medial prefrontal cortex (defined as the neocortical area innervated by the thalamic mediodorsal nucleus) labelled cells were observed in the pyramidal layer of the CA1 field of Ammon's horn. Observations made using antidromic stimulation confirmed these results, and revealed that slow conduction velocity of the fibers of the hippocampal cells innervating the prefrontal cortex. Taken together, these data provide evidence for a direct projection of CA1 cells to the medial prefrontal cortex.

Animals↗

PubMed1986

In vivo voltammetric measurement of extracellular DOPAC levels in the anteromedial prefrontal cortex of the rat.

Differential pulse voltammetric recordings with carbon fiber electrodes performed in vivo in the anteromedial prefrontal cortex of the rat yielded 3 oxidation peaks at -100, +100 and +300 mV, respectively. Pharmacological manipulations revealed that 3,4-dihydroxyphenylacetic acid (DOPAC) is the main contributor to the oxidation current recorded at +100 mV (peak 2). Thus, systemic administration of FLA 63 did not alter whereas pargyline caused a disappearance of cortical peak 2. Moreover, haloperidol and sulpiride increased peak 2 amplitude both in normal and in N-(2-chloroethyl)N-ethyl-2-bromobenzylamine (DSP4)-lesioned rats. Peak 2 was detected only in those prefrontal cortex regions known to receive a dopamine input. It is concluded that in vivo voltammetry with carbon fiber electrodes is a useful means of monitoring dopaminergic activity in the prefrontal cortex of the rat.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study.

The distribution of tyrosine hydroxylase (TH)-immunoreactive fibers was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density and/or laminar distribution of TH-labeled fibers were detected both across and within almost every prefrontal cytoarchitectonic region. In cynomolgus monkeys, areas 9 and 24 had the greatest density of TH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and areas 10 and 46 had the lowest density of immunoreactive fibers. Differences in fiber density within many of these regions were also consistently observed. On a laminar basis, the distribution of labeled fibers in a given area of cynomolgus prefrontal cortex was systematically related to the overall fiber density of that area. For example, in the lightly innervated fundus of the principal sulcus (area 46), labeled fibers were primarily present in layer I and layers V-VI, whereas in area 9, the most densely innervated region, TH-labeled fibers were present in all cortical layers. Similar regional differences in the density and laminar distribution of TH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. In previous studies, we have analyzed the regional and laminar distributions of fibers immunoreactive for TH and dopamine-beta-hydroxylase (DBH), a specific marker for noradrenergic cortical fibers, in multiple areas of cortex from both normal and locus ceruleus-lesioned animals. These comparisons, which have been confirmed in the present report, indicate that anti-TH and anti-DBH label distinct populations of axons in monkey neocortex, which presumably are dopaminergic and noradrenergic, respectively. Thus, the distribution of TH immunoreactivity described in the present report suggests that dopaminergic fibers are distributed in a very heterogeneous fashion in monkey prefrontal cortex. The distinctive innervation patterns exhibited by these fibers reveal the regions and layers that may be the principle sites of action of dopamine in exerting its effects on prefrontal cortical function.

Animals↗

PubMed1991

Neuronal activity related to saccadic eye movements in the monkey's dorsolateral prefrontal cortex.

1. Single-neuron activity was recorded from the prefrontal cortex of monkeys performing saccadic eye movements in oculomotor delayed-response (ODR) and visually guided saccade (VGS) tasks. In the ODR task the monkey was required to maintain fixation of a central spot throughout the 0.5-s cue and 3.0-s delay before making a saccadic eye movement in the dark to one of four or eight locations where the visual cue had been presented. The same locations were used for targets in the VGS tasks; however, unlike the ODR task, saccades in the VGS tasks were visually guided. 2. Among 434 neurons recorded from prefrontal cortex within and surrounding the principal sulcus (PS), 147 changed their discharge rates in relation to saccadic eye movements in the ODR task. Their response latencies relative to saccade initiation were distributed between -192 and 460-ms, with 22% exhibiting presaccadic activity and 78% exhibiting only postsaccadic activity. Among PS neurons with presaccadic activity, 53% also had postsaccadic activity when the monkey made saccadic eye movements opposite to the directions for which the presaccadic activity was observed. 3. Almost all (97%) PS neurons with presaccadic activity were directionally selective. The best direction and tuning specificity of each neuron were estimated from parameters used to fit a Gaussian tuning curve function. The best direction for 62% of the neurons with presaccadic activity was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (23%) or along the vertical meridian (15%). 4. Most postsaccadic activity of PS neurons (92%) was also directionally selective. The best direction for 48% of these neurons was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (36%) or along the vertical meridian (16%). Eighteen percent of the neurons with postsaccadic activity showed a reciprocal response pattern: excitatory responses occurred for one set of saccade directions, whereas inhibitory responses occurred for roughly the opposite set of directions. 5. Sixty PS neurons with saccade-related activity in the ODR task were also examined in a VGS task. Forty of these neurons showed highly similar profiles of directional specificity and response magnitude in both tasks, 13 showed saccade-related activity only in the ODR task, and 7 changed their response characteristics between the ODR and VGS tasks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Cations decrease specific [3H]-spiroperidol binding in human prefrontal cortex.

Ligand binding at many physiologically relevant receptors is regulated by divalent cations. To determine whether [3H]-spiroperidol binding sites in prefrontal cortex might be physiologically relevant receptors, we examined the effect of ions on the binding of this ligand in postmortem human prefrontal cortex. Our results indicate that several cations decreased [3H]-spiroperidol binding in a dose-dependent fashion. Of these, Cd++ and Zn++ were the most able to decrease [3H]-spiroperidol binding with IC50 of 5.5 +/- 2.4 X 10(-6)M and 5.6 +/- 1.1 X 10(-5)M respectively. These findings indicate that [3H]-spiroperidol may bind at physiologically relevant receptors in human prefrontal cortex.

Butyrophenones↗

PubMed1992

Electrophysiological influences of the parietal cortex and dorso-medial thalamic nucleus on the prefrontal cortex of the cat.

Lesion studies have shown that the functional integrity of prefrontal and posterior parietal cortex is necessary for complex behavioural performance. Recordings were made from 137 prefrontal cells in awake cats. Parietal cortex stimulation affected fifty-four cells (39.5%); thirty-four (63%) increased and twenty (37%) decreased their discharge frequency. Thalamic stimulation affected forty-seven cells; twenty-eight increased their discharge and nineteen decreased it. These responses suggest firstly that the organization between parietal and prefrontal cortex is similar to that in monkeys, and secondly that prefrontal cortex has an integrative role.

Animals↗

PubMed1984

Single neuron activity in dorsolateral prefrontal cortex of monkey during operant behavior sustained by food reward.

The activity of 190 neurons was recorded from the dorsolateral prefrontal cortex of monkeys during an operant task that consisted of 3 phases: visual discrimination of food and non-food, bar pressing to gain access to the food and ingestion. In area 8, a fairly large proportion of the 49 recorded neurons responded in both the visual discrimination (37%) and motor initiation (35%) phases. Some functional heterogeneity seems evident within area 8 since visual discrimination responses were rostral, visuokinesis was central and motor initiation was in the caudal bank of the arcuate sulcus. Neurons in area 9 responded primarily (37%) during the bar pressing phase and less during the visual discrimination phase. Neurons in area 10 responded variously during most phases of the task--food discrimination, bar pressing, and ingestion. Neurons in the periprincipal sulcal area usually responded in the visual discrimination phase, but some which did not respond to food presented in front of the subject responded to meaningful visual or auditory cues that were related to food reward. The data suggest that neurons in the dorsolateral prefrontal cortex have multiple functions related to all phases of complex, learned feeding behavior. Functional roles of the prefrontal cortex and the lateral hypothalamus in development of feeding behavior are discussed.

Animals↗

PubMed1983

Putative amino acid neurotransmitters and the nucleus dorsomedialis thalamus-prefrontal cortex pathway in the rat.

Endogenous levels of putative amino acid neurotransmitters (glycine, glutamic acid, aspartic acid, and GABA) in medial and sulcal prefrontal cortex of the rat were analyzed using gas liquid chromatography. No changes were found in the levels of these amino acids in medial and sulcal prefrontal cortex after lesion of the nucleus dorsomedialis of the thalamus suggesting, therefore, that the NDMT-prefrontal cortex pathway is not mediated by these amino acids.

Amino Acids↗