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Results for “Prefrontal Cortex”

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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↗

PubMed2000

Multiple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex.

Short-term synaptic plasticity, in particular short-term depression and facilitation, strongly influences neuronal activity in cerebral cortical circuits. We investigated short-term plasticity at excitatory synapses onto layer V pyramidal cells in the rat medial prefrontal cortex, a region whose synaptic dynamic properties have not been systematically examined. Using intracellular and extracellular recordings of synaptic responses evoked by stimulation in layers II/III in vitro, we found that short-term depression and short-term facilitation are similar to those described previously in other regions of the cortex. In addition, synapses in the prefrontal cortex prominently express augmentation, a longer lasting form of short-term synaptic enhancement. This consists of a 40-60% enhancement of synaptic transmission which lasts seconds to minutes and which can be induced by stimulus trains of moderate duration and frequency. Synapses onto layer III neurons in the primary visual cortex express substantially less augmentation, indicating that this is a synapse-specific property. Intracellular recordings from connected pairs of layer V pyramidal cells in the prefrontal cortex suggest that augmentation is a property of individual synapses that does not require activation of multiple synaptic inputs or neuromodulatory fibers. We propose that synaptic augmentation could function to enhance the ability of a neuronal circuit to sustain persistent activity after a transient stimulus. This idea is explored using a computer simulation of a simplified recurrent cortical network.

2-Amino-5-phosphonovalerate↗

PubMed2000

Is benzodiazepine-induced amnesia due to deactivation of the left prefrontal cortex?

UNLABELLED: The amnesic properties of benzodiazepines result from an impairment in explicit (conscious) acquisition of new material. RATIONALE: Explicit encoding of new material has consistently resulted in an increase in regional cerebral blood flow (rCBF) in the left prefrontal cortex, as measured by positron emission tomography (PET). OBJECTIVE: PET was used to determine whether an amnesic dose of midazolam (0.075 mg/kg) attenuated activation in this area during explicit memory encoding. METHODS: A second condition (condition A) used a task to control for the automatic processing that occurs during explicit learning (condition E). RESULTS: The subjects who received midazolam (n=7) recognised significantly fewer words than those who received placebo (n=8), but were not impaired with regard to automatic processing. rCBF was significantly increased in the left prefrontal cortex during explicit encoding of word lists in all subjects and in the temporal lobe and parieto-occipital regions during automatic processing. rCBF was significantly decreased in the prefrontal, superior temporal and parieto-occipital regions following midazolam. The midazolam-induced deactivation in the prefrontal cortex did not affect rCBF activations induced by the explicit memory condition (E-A). CONCLUSIONS: These results suggest that a specific interaction with prefrontal cortex activation does not underlie the amnesic effect of midazolam. However, it remains possible that a threshold level of prefrontal rCBF is necessary for encoding and that, after midazolam, this was not reached.

Adult↗

PubMed2004

The prefrontal cortex and working memory: physiology and brain imaging.

Sustained activity has been recorded in the prefrontal cortex during working memory tasks. First, we compare the anatomical distribution of this activity in humans and monkeys. Then, we show that it reflects many factors, maintenance of the items presented, preparation for the response, transformation of the items during the delay, task rules and task goals. Finally, we point out that sustained activity has also been recorded in other areas, such as the parietal cortex. We suggest that the key to prefrontal cortex lies not in the maintenance of sensory information but in the prospective use of that information for behaviour.

Animals↗

PubMed2000

Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo.

An intact mesocortical dopaminergic (DA) input to the prefrontal cortex (PFC) has been reported to be necessary for long-term potentiation (LTP) to occur at hippocampal-prefrontal cortex synapses. Here, we investigated the role of D1 and D2 receptors in this NMDA receptor-dependent LTP. Local infusion of the D1 agonist SKF81297 at an optimal dose induced a sustained enhancement of hippocampal-PFC LTP, whereas the D1 antagonist SCH23390 caused a dose-related impairment of its induction. The D1 agonist effect was mimicked by infusion of a low dose of the adenylyl cyclase activator forskolin, whereas LTP was severely attenuated with a protein kinase A inhibitor, Rp-cAMPS. To further assess the complex interplay between DA and NMDA receptors, changes in extracellular DA levels in the PFC were estimated during LTP, and a significant increase was observed immediately after tetanus. Taken together, these data suggest that D1 but not D2 receptors are crucial for the DA control of the NMDA receptor-mediated synaptic response on a specific excitatory input to the PFC. The interactions of these receptors may play a crucial role in the storage and transfer of hippocampal information in the PFC.

Animals↗

PubMed1997

Response learning of rats in a Morris water maze: involvement of the medical prefrontal cortex.

This study is concerned with the question whether the medial prefrontal cortex mediates spatial navigation requiring the expression of response learning. It consists of two parts. In the first experiment it was investigated whether intact male Wistar rats can learn a spatial response task in a Morris water maze, and, if so, how the learning of this task compares with the learning of a place task, in the same water maze. The data illustrate that rats can indeed learn the response task demands, but also demonstrate that this task is more difficult to learn than the place task. This is evidenced by a slower and more capricious acquisition. Based on these findings a second experiment was conducted, in which sham-operated rats and rats with damage of the medial prefrontal cortex (mPFC) were compared for their acquisition in the response task in the Morris water maze. The results showed that both escape latency and path length of the mPFC-damaged animals were significantly higher than those of the sham-operated animals. A behavioral analysis of the swimming paths demonstrated that the mPFC-damaged rats were more persistent in their use of a place strategy, while the sham-operated animals sooner switched to the more successful taxon-orientation strategy. Taken together with previous findings these data support the hypothesis of a functional dissociation of the mPFC with regard to its involvement in the expression of place and response learning.

Animals↗

PubMed1995

Fetal alcohol exposure alters the induction of immediate early gene mRNA in the rat prefrontal cortex after an alternation task.

The present study examined fetal alcohol effects (FAE) on the induction of the immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the prefrontal cortex, hippocampus, and other brain regions after testing in an alternation task. Subjects were female offspring of Sprague-Dawley rats fed either a 35% ethanol-derived calorie diet, pair-fed with sucrose, or control-fed with laboratory chow during the last week of gestation. At 75-85 days of age, rats were food-deprived and trained in a t-maze for food reward. Then rats were tested at 5-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed 30 min after testing. The remaining animals were killed from their home cage and acted as controls. Expression of the four IEG mRNAs was examined in the brains of these animals using in situ hybridization. FAE rats showed a memory deficit at the 60-sec delay (p < 0.05), but not at the 0-sec or 30-sec delays. Testing in the alternation task induced a significant elevation of c-fos, c-jun, jun B, and zif268 mRNA expression in the prefrontal cortex, hippocampal subfields CA1 and CA3, and several cortical areas. However, FAE rats showed a significantly smaller elevation of both c-fos and jun B mRNA levels in the orbital, prelimbic, and anterior cingulate regions of the prefrontal cortex (p < 0.05). FAE animals also showed a lower expression of jun B mRNA in the caudate nucleus. Significant correlations between the mean performance at the 60-sec delay and mRNA expression of c-fos, jun B, and zif268 in the prefrontal cortical regions (p < 0.05) were observed. These findings suggest that fetal alcohol exposure produces changes in the adult prefrontal cortex that may contribute to the behavioral deficit in the alternation task.

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↗

PubMed1993

A connectionist approach to the prefrontal cortex.

Recent data from studies of the prefrontal cortex (PFC) in humans and laboratory animals are reviewed with particular reference to the anatomical substrates of prefrontal neuropsychological function in health and disease. The PFC has been shown to have a unique pattern of supramodal connectivity with intracortical and subcortical circuits that place the PFC in an anatomical position to subserve "executive" cognitive functions and modulate limbic information to relate to basal ganglia circuits in a highly specific manner and to uniquely control the neurochemical elements of attention and reward. PFC connectivity is also consistent with current hypotheses about prefrontal neuropsychology, which emphasize conscious, goal-directed behavior guided by past experience. PFC connectivity explains the frequency with which prefrontal dysfunction is seen in disease states, which, on the basis of neuroimaging and neuropathology data, can be categorized as either intrinsic or dysconnection disorders.

Basal Ganglia↗

PubMed2005

Egocentric spatial orientation in a water maze by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex.

The acquisition of a water maze based task requiring egocentric spatial orientation in the absence of distal cues was studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats that received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham-operated control group. Isolated lesions of both the anteromedial prefrontal cortex and the hippocampus were associated with a significantly impaired task acquisition. Both of these individually lesioned groups did, however, eventually demonstrate full functional recovery by reaching the task proficiency of the sham-operated control group. In contrast, the group in which both of these structures had been lesioned failed to demonstrate full functional recovery and was severely and long-lastingly impaired when compared to all other groups. Behavioural challenges in the form of a no-platform session and two reversals of platform position demonstrated that while the sham-operated control group and the group subjected to fimbria-fornix transections in isolation utilized rather pure egocentric orientation strategies, the two prefrontally lesioned groups (and especially the combined lesion group) employed a different set of solution strategies which at least partly relied on a "circling" method. Even in the behaviour of the prefrontally lesioned groups, however, indications of a certain level of cognitive representations of the platform positions were seen. It is concluded that both the prefrontal cortex and the hippocampus contribute to the mediation of egocentric spatial orientation. Furthermore, the hippocampus is a significant and potentially irreplaceable part of the neural substrate of functional recovery of the presently studied task after prefrontal lesions--while the prefrontal cortex may play a similar role with respect to hippocampal lesions.

Animals↗

PubMed2006

Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia.

BACKGROUND: Studies suggest that neuronal density in left dorsolateral prefrontal cortex is increased in schizophrenia. AIMS: To replicate these findings and extend them to both hemispheres. METHOD: Neuronal density, size and shape were estimated in the prefrontal cortex (Brodmann area 9) of the left and right hemispheres of brains taken post-mortem from 10 people with schizophrenia and 10 without mental illness (6 men, 4 women in both groups). RESULTS: Overall neuronal density (individually corrected for shrinkage) did not differ between the groups. In the control brains, density was generally greater in the left than the right hemisphere, the reverse was seen in the schizophrenia brains; this loss or reversal of asymmetry was most significant in cortical layer 3. Pyramidal neurons in this cell layer were significantly larger on the left and more spherical in shape than on the right side in control brains, but size and shape did not differ between the two sides in schizophrenia. Non-pyramidal and glial cell densities were unchanged. CONCLUSIONS: We failed to find an increase in neuronal density, but found evidence at a cellular level of loss or reversal of asymmetry, consistent with the hypothesis of a primary change in the relative development of areas of heteromodal association cortex in the two hemispheres.

Aged↗

PubMed1997

Ibotenic acid lesions of prefrontal cortex do not prevent expression of behavioral sensitization to amphetamine.

We have shown previously that ibotenic acid lesions of the prefrontal cortex, performed prior to repeated amphetamine administration, do not affect sensitization of stereotyped behaviors but do prevent sensitization of post-stereotypy locomotor hyperactivity [Wolf et al., Neuroscience, 69 (1995) 417-439]. This could reflect an effect of the lesion on either development or expression of locomotor sensitization. To test the latter possibility, rats were treated with repeated amphetamine injections and tested to establish behavioral sensitization. Then, half received ibotenic acid lesions of prefrontal cortex and half received sham lesions. A second amphetamine challenge, 7 days later, demonstrated that the lesion failed to prevent expression of sensitization. Together with previous results, this suggests that intrinsic neurons of prefrontal cortex, most likely those sending excitatory amino acid-containing projections to the ventral tegmental area, are required for the development but not the expression of behavioral sensitization to amphetamine.

Amphetamine↗

PubMed1998

Nitric oxide synthase and the acetylcholine receptor in the prefrontal cortex: metasynaptic organization of the brain.

Nitric oxide synthase (NOS) and the nicotinic acetylcholine receptor (nAChR) immunoreactivity of the cerebral cortex was studied in adult Macaca fascicularis monkeys at light- and electron microscopic levels. NOS was located by means of the polyclonal antibodies developed by Transduction Laboratories (Lexington, KY, USA), as primary serum, in a dilution of 1:1000, and nAChR was located by means of biotinylated alpha-bungarotoxin (BTX) obtained from Molecular probes (Eugene, Oregon, USA) in a dilution of 1:2000. While endothelial eNOS outlined blood vessels in the brain, brain-derived (neural) bNOS labelled three well-defined cell types in area 46 of the prefrontal cortex, viz. (a) bipolar cells, scattered through layers III to V, equipped with long dendrites which pass over the thickness of the cortex in a right angle to the pial surface, establishing dendritic bundles closely reminiscent of a columnar organization; (b) large multipolar cells, located mainly in layers V and VI, with axons which interconnect dendritic bundles of the bipolar cells and establish synapses with dendritic shafts and spines of the former; and (c) stellate cells, located in lamina II and III, which establish an axonal network in lamina zonalis (lamina I). This arrangement is most characteristic in area 46 of the prefrontal cortex; areas 10 and 12 display similar features. In contrast, the primary visual cortex (area 17), is lacking any sign of columnar organization. Localization of bNOS immunoreactivity is at marked variance to that of NADPH-diaphorase which labels large pyramidal cells in the primate cortex. Binding of alpha-bungarotoxin (BTX) which labels the alpha 7 subunit of nAChR is located in somata, dendrites and axons of interneurons scattered over the entire width of the prefrontal cortex; on the other hand, the monoclonal antibody mAb 35 which labels subunits alpha 1, alpha 3 and alpha 5 in the main immunogenic region of the receptor, visualizes apical dendritic shafts similar to those like bNOS. Strategic localization of bNOS in the primate prefrontal cortex fulfills criteria of producing a freely diffusing retrograde messenger molecule operative in signal transduction routes subserving topography and columnar organization of the cortex, as well as long-term potentiation and long-term depression phenomena underlying mnemonic and gnostic functions. Common occurrence of bNOS and nAChR in identical or similar structures in the prefrontal cortex suggests that interactions between nitrogen oxide and presynaptically released acetylcholine might be involved in the metasynaptic organization of the cerebral cortex, operating in a non-synaptic manner in maintaining optimal performance on cognitive tasks.

Animals↗

PubMed1994

Lesion induced expression of low-affinity NGF-binding protein (p75) immunoreactivity after neonatal and adult aspiration lesions of the rat dorsomedial prefrontal cortex.

The present study was performed in order to examine whether or not NGF-mediated processes could be involved in the sparing of function observed after neonatal prefrontal cortex lesions. After unilateral neonatal aspiration lesions of the dorsomedial prefrontal cortex, fibers immunoreactive for the low-affinity NGF-binding protein (p75) with a deviant morphology were observed in the severed hemisphere only. The morphology of these fibers was characterized by their large caliber, their large, often bulbous varicosities, and their curly appearance. These fibers were present as soon as 24 h after the operation. Between 3 and 5 days after the operation, the greatest abundance of these fibers was found in the ventrorostral areas of the forebrain and along the pathways of cortical projections of the cholinergic cell groups. After 7 days, such fibers were no longer observed. After comparable lesions in adult animals, a similar type of fiber was observed in the lesioned hemisphere. However, in these cases a response comparable to that observed in the neonatal animals was not observed until 5 days after the operation, with fewer fibers. Furthermore, in contrast to what was observed after neonatal lesions, in adult animals no indications of retrograde transport of p75 immunoreactive material towards the cholinergic cells of the basal forebrain nuclei were found. From these findings it was concluded that the prompt upregulation of p75 expression in neonatal animals may contribute to the survival of the cholinergic cells of the basal forebrain, and may therefore be involved in the restoration of function of the medial prefrontal cortex.

Aging↗

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↗

PubMed1996

Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex.

Rapid-rate transcranial magnetic stimulation (rTMS) was administered to 10 healthy volunteers on different days over the right or left prefrontal cortex, midfrontal cortex, occipital cortex, or cerebellum. Mood (self-rated), reaction time, and hormone levels were serially measured. Consistent with a previous study, comparison of hemispheres revealed significant associations with decreased happiness after left prefrontal rTMS and decreased sadness after right prefrontal rTMS. Stimulation of all three prefrontal regions, but not the occipital or cerebellar regions, was associated with increases in serum thyroid-stimulating hormone. There was no effect on serum prolactin. rTMS applied to prefrontal cortex is safe and well tolerated and produces regionally and laterally specific changes in mood and neuroendocrine measures in healthy adults. rTMS is a promising tool for investigating prefrontal cortex functions.

Adult↗

PubMed2003

The role of the prefrontal cortex in object-place learning: a test of the attribute specificity model.

In order to test an attribute specificity model of prefrontal cortex function, rats with lesions in the prelimbic-infralimbic (PL-IL) or anterior cingulate and precentral (AC-PC) subregions of the medial prefrontal cortex and controls were trained on an object-place paired associate task. Rats with AC-PC lesions acquired the task as readily as controls. In contrast, the PL-IL lesioned rats did not learn the task. Whenever higher order processing is required to solve a task, the data support an attribute-specificity model of prefrontal cortex function in that the PL-IL cortices support both object and place attribute information in a variety of tasks including object-place paired associate learning.

Animals↗

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↗