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Results for “Prefrontal Cortex”

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PubMed2002

Selective reduction by dopamine of excitatory synaptic inputs to pyramidal neurons in primate prefrontal cortex.

We have employed in vitro physiological methods to investigate dopaminergic modulation of excitatory synaptic transmission in monkey prefrontal cortex (PFC) circuits. We show that combined activation of D1-like and D2-like dopamine receptors results in the reduction of extracellular stimulation-evoked isolated EPSCs in layer 3 pyramidal neurons. Using paired recordings from synaptically connected pyramidal neurons we have determined the basic properties of unitary synaptic connections between layer 3 pyramids in the primate PFC and, interestingly, we found that dopamine does not reduce synaptic transmission between nearby pairs of synaptically coupled PFC pyramidal neurons. This input specificity may be a critical aspect of the dopaminergic regulation of recurrent excitatory circuits in the PFC.

Animals↗

PubMed1997

Repeated cocaine and stress increase dopamine clearance in the rat medial prefrontal cortex.

The effects of repeated footshock stress or cocaine on the kinetics of dopamine clearance in the medial prefrontal cortex (mPFC) were measured by rotating disk electrode voltammetry (RDEV). Five groups of rats were used: animals were either naive (non-handled), pre-treated with five daily saline (1 ml/kg i.p.) or cocaine (15 mg/kg i.p.) injections, or pre-treated with five daily 20-min sessions of sham shock or footshock (0.05 mA/200 ms/s). Dopamine clearance was measured after a 1-week withdrawal period. No difference in Km values was present among the treatment groups, with the mean Km value at approximately 0.5 microM for all groups. However, Vmax values were approximately 50% higher in daily sham shock-, footshock- and cocaine-pre-treated animals compared to naive rats. The increased ability to remove dopamine in these animals suggests that altered dopamine clearance may serve an adaptive mechanism in the mPFC.

Animals↗

PubMed1992

A comparison of normal old rats and young adult rats with lesions to the hippocampus or prefrontal cortex on a test of matching-to-sample.

Rats with lesions to the dorsal hippocampus (HPC) or prefrontal cortex (PFC), normal old rats, and young adult controls were compared on a test of matching-to-sample. Subjects were presented with two lights in succession and were trained to press a lever when the lights were the same brightness and withhold a lever-press when they were different. The PFC and aged groups, but not the HPC group, were impaired when the comparison stimulus was presented immediately after the sample stimulus. When delays of 5 and 15 sec were introduced between the stimuli, the HPC and aged groups' performance deteriorated to chance levels. The PFC group's performance was not differentially affected by the delays. The results were consistent with previous findings that implicated the HPC in episodic memory and the PFC in working memory. The aged group was impaired on both types of memory, revealing signs of HPC and PFC dysfunction.

Aging↗

PubMed2005

A role for prefrontal cortex in the extinction of a conditioned taste aversion.

This study used immunohistochemical methods to determine if the medial prefrontal cortex (mPFC) is involved in the extinction of a conditioned taste aversion (CTA). As rats reached 90% reacceptance of a tastant (saccharin: SAC) that had previously been associated with lithium chloride-induced malaise, c-Fos protein expression increased dramatically as compared to animals with active CTAs, animals without CTAs (i.e., explicitly unpaired CS-US exposures) or animals drinking SAC for the first time. These data indicate a role for mPFC (prelimbic and infralimbic cortex) in the formation of a CTA extinction memory.

Animals↗

PubMed1998

Functional dissociation of the prefrontal cortex and the hippocampus in timing behavior.

Using the peak procedure, rats with aspiration lesions to the medial prefrontal cortex (PFC) or the hippocampus were tested for the acquisition of timing behavior and temporal memory. After surgery, rats were 1st trained to discriminate a 40-s interval and then tested for temporal memory with gap trials. Results indicated that lesions to the medial PFC disrupted the acquisition of timing behavior. Medial PFC animals needed significantly more trials to reach criterion, and their temporal discrimination function was less uniform and steep, indicating a general deficit in timing ability. In hippocampal rats, the ability to estimate the duration of the discriminative stimulus was unaffected by the lesion. It was concluded that the hippocampus is not necessary for the acquisition of timing behavior in this task. Gap trials failed to produce a deficit in the memory for temporal events for either lesion. Thus, it was further concluded that neither the medial PFC nor the hippocampus is necessary for the memory of temporal events.

Analysis of Variance↗

PubMed1994

Involvement of subdivisions of the medial prefrontal cortex in learned cardiac adjustments in rabbits.

Electrical stimulation of area 24 and area 32 of the medial prefrontal cortex (mPFC) in rabbits elicited increases in respiration rate and decreases in heart rate (HR) and blood pressure. However, stimulation in area 25 elicited pressor responses and a biphasic HR response consisting of an initial HR increase followed by an HR decrease. Administration of an alpha-adrenergic receptor antagonist eliminated the pressor response and bradycardiac response produced by area 25 stimulation but it had no effect on the bradycardia elicited by stimulation of area 24 or area 32. Lesions centered on area 32 of the mPFC greatly attenuated the conditioned bradycardiac response elicited by paired tone and paraorbital shock presentations. Lesions of area 24 produced a decrease in discrimination between a reinforced conditioned stimulus and a nonreinforced conditioned stimulus but had no effect on the magnitude of the conditioned response. Area 25 lesions had no effect on any aspect of conditioned responding.

Animals↗

PubMed1995

Postnatal maturation of layer V pyramidal neurons in the human prefrontal cortex. A quantitative Golgi analysis.

The pattern of dendritic development of layer V pyramidal neurons in the human prefrontal cortex was studied quantitatively. The main objective was to determine how dendritic growth and differentiation continued postnatally. In order to do this, we analyzed the three-dimensional branching pattern of the basal dendritic field of Golgi-Cox impregnated neurons. The subjects ranged in age from 7.5 months after birth up to 27 years. The results revealed a maturational time-course with a rapid dendritic growth phase during the first postnatal year. The dendritic length and radial extension of the basal field increased. The growth continued, at a reduced rate, up to around 5 years of age by a lengthening of the terminal segments and a slight increase in soma size. The morphological maturation of the layer V pyramidal neurons was completed between one and five years. After this age the dendritic values appeared to level off and reach a stable level that lasted up to at least 27 years. This paper gives no indications for overgrowth or regressive events of the layer V basal dendritic trees during development.

Adolescent↗

PubMed2006

Role of the prefrontal cortex in the foreperiod effect: TMS evidence for dual mechanisms in temporal preparation.

The involvement of right dorsolateral prefrontal cortex (rDLPFC) in explicit temporal processing is well documented. Conversely, the role of this area in implicit temporal processing (e.g., foreperiod [FP] effect) is still poorly understood. The FP effect, usually observed when a range of variable FPs occur randomly and equiprobably, consists of reaction times (RTs) decreasing as the FP increases. Moreover, in such paradigms, RTs increase as a function of the preceding FP (i.e., sequential effects). Patients with lesions of the rDLPFC do not show the typical FP effect. The present study aimed to replicate these results in healthy adults using transcranial magnetic stimulation (TMS) and to further investigate whether any change of sequential effects follows a reduction of the FP effect. The results of 2 experiments (with simple and choice RT tasks, respectively) indicate that the FP effect was significantly reduced after TMS over the rDLPFC, whereas no effect was observed after stimulation of a left contralateral site and the right angular gyrus. Conversely, sequential effects were not influenced by TMS. A dual-process model of the FP phenomena is proposed to interpret the dissociation found between the 2 effects.

Adult↗

PubMed2005

Neuronal activity representing temporal prediction of reward in the primate prefrontal cortex.

Temporal prediction of future events, especially regarding reward delivery, is critical for controlling/learning purposeful behavior. The dorsolateral prefrontal cortex (DLPFC) has been considered to be involved in behavioral control based on prospective coding for future events, including reward. Thus this area is likely to have a neuronal mechanism responsible for temporal prediction of forthcoming reward. To address this hypothesis, we recorded the neuronal activity from the DLPFC of macaque monkeys while they performed an oculomotor delayed-response task under two conditions regarding the time of reward delivery. In this task, when the subjects made a correct response, the reward was delivered after a reward-delay period of 0.5 or 2 s. At the behavioral level, the onset latency for saccades was significantly faster in the shorter reward-delay trials (0.5 s) than in longer reward-delay trials (2 s), indicating that our subjects actually predicted the time of reward delivery. At the neuronal level, we found that many DLPFC neurons showed differential activity depending on the predicted time of reward delivery during the cue and/or delay periods. These results suggest that a fraction of neurons in the DLPFC represent the temporal prediction of reward and probably a variety of other future events.

Action Potentials↗

PubMed1984

Topography of commissural fibers of the prefrontal cortex in the rhesus monkey.

The topography of commissural fibers of the prefrontal cortex was studied in the rhesus monkey using autoradiography. Commissural fibers originating in the medial prefrontal and the caudal orbital regions course through the anterior portion of the genu and the rostrum of the corpus callosum, while those from the arcuate concavity travel at the rostral border of the body of the corpus callosum. Fibers emanating from the peri-principalis region occupy an intermediate position in the genu of the corpus callosum.

Animals↗

PubMed2000

The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.

This paper reviews architectonic subdivisions and connections of the orbital and medial prefrontal cortex (OMPFC) in rats, monkeys and humans. Cortico-cortical connections provide the basis for recognition of 'medial' and 'orbital' networks within the OMPFC. These networks also have distinct connections with structures in other parts of the brain. The orbital network receives sensory inputs from several modalities, including olfaction, taste, visceral afferents, somatic sensation and vision, which appear to be especially related to food or eating. In contrast, the medial network provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. The two networks have distinct connections with areas of the striatum and mediodorsal thalamus. In particular, projections to the nucleus accumbens and the adjacent ventromedial caudate and putamen arise predominantly from the medial network. Both networks also have extensive connections with limbic structures. Based on these and other observations, the OMPFC appears to function as a sensory-visceromotor link, especially for eating. This linkage appears to be critical for the guidance of reward-related behavior and for setting of mood. Imaging and histological observations on human brains indicate that clinical depressive disorders are associated with specific functional and cellular changes in the OMPFC, including activity and volume changes, and specific changes in the number of glial cells.

Animals↗

PubMed1998

Glutamatergic regulation of basal and stimulus-activated dopamine release in the prefrontal cortex.

The present study was undertaken to determine whether basal and stimulus-activated dopamine release in the prefrontal cortex (PFC) is regulated by glutamatergic afferents to the PFC or the ventral tegmental area (VTA), the primary source of dopamine neurons that innervate the rodent PFC. In awake rats, blockade of NMDA or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in the VTA, or blockade of AMPA receptors in the PFC, profoundly reduced dopamine release in the PFC, suggesting that the basal output of dopamine neurons projecting to the PFC is under a tonic excitatory control of NMDA and AMPA receptors in the VTA, and AMPA receptors in the PFC. Consistent with previous reports, blockade of cortical NMDA receptors increased dopamine release, suggesting that NMDA receptors in the PFC exert a tonic inhibitory control on dopamine release. Blockade of NMDA or AMPA receptors in the VTA as well as blockade of AMPA receptors in the PFC reduced the dopaminergic response to mild handling, suggesting that activation of glutamate neurotransmission also regulates stimulus-induced increase of dopamine release in the PFC. In the context of brain disorders that may involve cortical dopamine dysfunction, the present findings suggest that abnormal basal or stimulus-activated dopamine neurotransmission in the PFC may be secondary to glutamatergic dysregulation.

2-Amino-5-phosphonovalerate↗

PubMed1996

Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially alter subcortical dopamine utilization and the behavioral response to stress.

The effects of left and right prefrontal cortical dopamine (DA) depletion on circling behavior, stress-escape behavior and subcortical DA function were examined in rats exhibiting left or right turning biases. 6-Hydroxydopamine lesions of the medial prefrontal cortex (PFC) caused significant DA depletions when assessed in separate studies at 3 days and 3-4 weeks. However, depletions were smaller at 3-4 weeks and there was a significant increase in DA concentration on the left side following right lesions. Significant increases in striatal DA content were observed following lesions of either side at 3-4 weeks, but not at 3 days. No changes in DA concentration were observed in the nucleus accumbens septi (NAS). Left circling rats significantly increased their circling behavior following right sided lesions and showed disrupted footshock-escape behavior following left sided lesions. Performance of the footshock-escape task exerted an effect on striatal and NAS DA utilization as indicated by the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to DA. The effects of footshock on NAS DA utilization were greater following left PFC lesions as compared to the right lesion and sham conditions. These lesion effects were also greater in left- than in right-turning animals. The data indicate that an intrinsic asymmetry in brain DA systems interacts with left and right PFC lesions to differentially determine subcortical DA function and behaviors that it subserves.

Animals↗

PubMed2001

Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance.

Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naive verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naive conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naive use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion.

Adult↗

PubMed2005

Functional network in the prefrontal cortex during episodic memory retrieval.

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.

Adult↗

PubMed2003

Semantic processing in the left inferior prefrontal cortex: a combined functional magnetic resonance imaging and transcranial magnetic stimulation study.

The involvement of the left inferior prefrontal cortex (LIPC) in phonological processing is well established from both lesion-deficit studies with neurological patients and functional neuroimaging studies of normals. Its involvement in semantic processing, on the other hand, is less clear. Although many imaging studies have demonstrated LIPC activation during semantic tasks, this may be due to implicit phonological processing. This article presents two experiments investigating semantic functions in the LIPC. Results from a functional magnetic resonance imaging experiment demonstrated that both semantic and phonological processing activated a common set of areas within this region. In addition, there was a reliable increase in activation for semantic relative to phonological decisions in the anterior LIPC while the opposite comparison (phonological vs. semantic decisions) revealed an area of enhanced activation within the posterior LIPC. A second experiment used transcranial magnetic stimulation (TMS) to temporarily interfere with neural information processing in the anterior portion of the LIPC to determine whether this region was essential for normal semantic performance. Both repetitive and single pulse TMS significantly slowed subjects' reactions for the semantic but not for the perceptual control task. Our results clarify the functional anatomy of the LIPC by demonstrating that anterior and posterior regions contribute to both semantic and phonological processing, albeit to different extents. In addition, the findings go beyond simply establishing a correlation between semantic processing and activation in the LIPC and demonstrate that a transient disruption of processing selectively interfered with semantic processing.

Adult↗

PubMed2006

Facilitation of glutamate release by nicotine involves the activation of a Ca2+/calmodulin signaling pathway in rat prefrontal cortex nerve terminals.

The effect of nicotine on evoked glutamate release from isolated nerve terminals (synaptosomes) from rat prefrontal cortex was examined. We found that nicotine significantly potentiated 4-aminopyridine (4AP)-evoked glutamate release, and this potentiatory effect was mimicked by the selective alpha7 nicotinic receptor agonist choline and was blocked by the selective alpha7 nicotinic receptor antagonist methyllycaconitine, indicating its mediation by alpha7 nicotinic receptors. Examination of the effect of nicotine on cytosolic [Ca(2+)] revealed that the potentiation of glutamate release was associated with an increase in voltage-dependent Ca(2+) influx through N- and P/Q-type Ca(2+) channels. The potentiatory effect of nicotine on Ca(2+) influx seems to be attributed to its increasing synaptosomal excitability because nicotine significantly increased depolarization-evoked increase in the intrasynaptosomal free Na(+) concentration and 4AP-evoked depolarization of the synaptosomal plasma membrane potential. Also, Ca(2+) ionophore ionomycin-induced glutamate release was enhanced by nicotine, and this action was blocked by methyllycaconitine. These results suggest that nicotine exerts its potentiatory effect presynaptically, likely through the activation of alpha7 nicotinic receptors, resulting in Na(+) influx and local depolarization, which subsequently enhances the Ca(K+) entry through voltage-dependent N-and P/Q-type Ca(2+) channels as well as the vesicular release machinery to cause an increase in evoked glutamate release from rat prefrontocortical nerve terminals. Moreover, in this release potentiation may involve an activation of Ca(2+)/calmodulin signaling pathway as nicotine-mediated potentiation of 4AP- and ionomycin-evoked glutamate release were significantly attenuated by KN62, a selective inhibitor of Ca(2+)/calmodulin-dependent kinase II.

4-Aminopyridine↗

PubMed2006

Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia.

Postmortem studies have revealed reduced densities of dendritic spines in the dorsal lateral prefrontal cortex (DLPFC) of subjects with schizophrenia. However, the molecular mechanisms that might contribute to these alterations are unknown. Recent studies of the intracellular signals that regulate spine dynamics have identified members of the RhoGTPase family (e.g., Cdc42, Rac1, RhoA) as critical regulators of spine structure. In addition, Duo and drebrin are spine-specific proteins that are critical for spine maintenance and spine formation, respectively. In order to determine whether the mRNA expression levels of Cdc42, Rac1, RhoA, Duo or drebrin are altered in schizophrenia, tissue sections containing DLPFC area 9 from 15 matched pairs of subjects with schizophrenia and control subjects were processed for in situ hybridization. Expression levels of these mRNAs were also correlated with DLPFC spine density in a subset of the same subjects. In order to assess the potential influence of antipsychotic medications on the expression of these mRNAs, similar studies were conducted in monkeys chronically exposed to haloperidol or olanzapine. The expression of each of these mRNAs was lower in the gray matter of the subjects with schizophrenia compared to the control subjects, although only the reductions in Cdc42 and Duo remained significant after corrections for multiple comparisons. In addition, spine density was strongly correlated with the expression levels of both Duo (r=0.73, P=0.007) and Cdc42 (r=0.71, P=0.009) mRNAs. In contrast, the expression levels of Cdc42 and Duo mRNAs were not altered in monkeys chronically exposed to antipsychotic medications. In conclusion, reduced expression of Cdc42 and Duo mRNAs may represent molecular mechanisms that contribute to the decreased density of dendritic spines in the DLPFC of subjects with schizophrenia.

Adult↗