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At least 19 recordsLinked to original sources
PubMed2005

Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex.

Prefrontal cortex is a target for glucocorticoids, shows neurochemical changes in response to stress and mediates many of the behaviors that are altered by chronic corticosterone administration. Three weeks of either daily corticosterone injections or 3 h daily restraint stress result in dendritic changes in pyramidal neurons in medial prefrontal cortex. Interestingly, vehicle injection results in similar but less pronounced changes. Thus, the mild stress of daily injections alone may alter morphology of medial prefrontal cortex, suggesting an exquisite sensitivity to chronic stress. To further examine this morphological sensitivity, we assessed the effect of 1 week of daily brief restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were restrained 10 min per day for one week, handled daily or left unhandled. Rats were then overdosed and brains were stained using a Golgi-Cox procedure. Layer II-III pyramidal neurons in medial prefrontal cortex were drawn and dendritic morphology was quantified. One week of daily brief restraint resulted in selective remodeling of apical dendrites, with atrophy of up to 22-35% in distal branches and sparing of proximal branches. This pattern of reorganization is similar to that seen after either corticosterone injections or 3 weeks of daily 3 h restraint stress. Thus, the stress-induced dendritic changes in medial prefrontal cortex occur rapidly, and in response to a mild stressor.

Adaptation, Physiological↗
PubMed2002

Filtering of neural signals by focused attention in the monkey prefrontal cortex.

Prefrontal cortex is thought to be important in attention and awareness. Here we recorded the activity of prefrontal neurons in monkeys carrying out a focused attention task. Having directed attention to one location, monkeys monitored a stream of visual objects, awaiting a predefined target. Although neurons rarely discriminated between one non-target and another, they commonly discriminated between targets and non-targets. From the onset of the visual response, this target/non-target discrimination was effectively eliminated when the same objects appeared at an unattended location in the opposite visual hemifield. The results show that, in prefrontal cortex, filtering of ignored locations is strong, early and spatially global. Such filtering may be important in blindness to unattended signals--a conspicuous aspect of human selective attention.

Animals↗
PubMed1989

Projections from inferior temporal cortex to prefrontal cortex via the uncinate fascicle in rhesus monkeys.

In five rhesus monkeys (Macaca mulatta) we used anterograde and retrograde tracing techniques to investigate the projection from the inferior temporal cortex (area TE) to the prefrontal cortex as well as the course of the projecting fibers. The results showed that TE projects to both the inferior convexity and orbital surface of prefrontal cortex and that these projections course almost exclusively via the uncinate fascicle. Transection of the uncinate fascicle deprives the prefrontal cortex of virtually all input from TE, but leaves intact inputs from prestriate and parietal visual areas as well as the amygdala. Such transection also leaves intact many projections from TE to targets other than the prefrontal cortex, including the amygdala, ventral putamen, tail of the caudate nucleus, and pulvinar.

Amino Acids↗
PubMed2005

Differential localization of protein phosphatase-1alpha, beta and gamma1 isoforms in primate prefrontal cortex.

Prefrontal cortical functioning depends on D1 family receptors and their complex signal transduction cascade, including protein phosphatase-1 (PP1). Three PP1 isoforms are prominent in the brain: PP1alpha, PP1beta and PP1gamma1. PP1 localization by a variety of scaffolding proteins is critical for dopamine-mediated modulation of glutamatergic neurotransmission. We have quantified the subcellular distribution of each isoform in primate prefrontal cortex using immunoelectron microscopy. All three are found in spines, dendrites, axon terminals, axons and glia. However, PP1alpha and PP1gamma1 labeling is enriched in spines, whereas PP1beta label is enriched in dendrites. Using post-embedding immunogold labeling, we further examined the distribution of PP1alpha and PP1gamma1 within spines. PP1gamma1 is highly and specifically concentrated in the postsynaptic density (PSD) of these spines, while PP1alpha is enriched in the PSD but also found subjacent to the PSD in moderate amounts. Thus, PP1 isoforms are heterogeneously distributed in the cortical neuropil and within spines. These results suggest that each PP1 isoform has access to a different set of substrates and, furthermore, they demonstrate that the composition of signal transduction proteins varies in different parts of the neuron and even in different regions of a dendritic spine in the primate PFC.

Animals↗
PubMed2006

Inverted-U profile of dopamine-NMDA-mediated spontaneous avalanche recurrence in superficial layers of rat prefrontal cortex.

Prefrontal cortex (PFC) functions, such as working memory, attention selection, and memory retrieval, depend critically on dopamine and NMDA receptor activation by way of an inverted-U-shaped pharmacological profile. Although single neuron responses in the PFC have shown some aspects of this profile, a network dynamic that follows the dopamine-NMDA dependence has not been identified. We studied neuronal network activity in acute medial PFC slices of adult rats by recording local field potentials (LFPs) with microelectrode arrays. Bath application of dopamine or the dopamine D1 agonist SKF38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride] in combination with NMDA induced spontaneous LFPs predominantly in superficial cortex layers. The LFPs at single electrodes were characterized by sharp negative peaks that were clustered in time across electrodes revealing diverse spatiotemporal patterns on the array. The pattern formation required fast GABAergic transmission, coactivation of the dopamine D1 and NMDA receptor, and depended in an inverted-U profile on dopamine. At moderate concentrations of dopamine or the dopamine D1 agonist, the pattern size distribution formed a power law with exponent alpha = -1.5, indicating that patterns are organized in the form of neuronal avalanches, thereby maximizing spatial correlations in the network. At lower or higher concentrations, alpha was more negative than -1.5, indicating reduced spatial correlations. Likewise, at moderate dopamine concentrations, the avalanche rate and recurrence of specific avalanches was maximal with recurrence frequencies after a "power law"-like heavy-tail distribution with a slope of -2.4. We suggest that the dopamine-NMDA-dependent spontaneous recurrence of specific avalanches in superficial cortical layers might facilitate integrative and associative aspects of PFC functions.

Action Potentials↗
PubMed2002

Mechanisms of dopamine activation of fast-spiking interneurons that exert inhibition in rat prefrontal cortex.

Prefrontal cortical dopamine (DA) modulates pyramidal cell excitability directly and indirectly by way of its actions on local circuit GABAergic interneurons. DA modulation of interneuronal functions is implicated in the computational properties of prefrontal networks during cognitive processes and in schizophrenia. Morphologically and electrophysiologically distinct classes of putative GABAergic interneurons are found in layers II-V of rat prefrontal cortex. Our whole cell patch-clamp study shows that DA induced a direct, TTX-insensitive, reversible membrane depolarization, and increased the excitability of fast-spiking (FS) interneurons. The DA-induced membrane depolarization was reduced significantly by D1/D5 receptor antagonist SCH 23390, but not by the D2 receptor antagonist (-)sulpiride, D4 receptor antagonists U101958 or L-745870, alpha1-adrenoreceptor antagonist prazosin, or serotoninergic receptor antagonist mianserin. The D1/5 agonists SKF81297 or dihydrexidine, but not D2 agonist quinpirole, also induced a prolonged membrane depolarization. Voltage-clamp analyses of the voltage-dependence of DA-sensitive currents, and the effects of changing [K(+)](O) on reversal potentials of DA responses, revealed that DA suppressed a Cs(+)-sensitive inward rectifier K(+) current and a resting leak K(+) current. D1/D5, but not D2 agonists mimicked the suppressive effects of DA on the leak current, but the DA effects on the inward rectifier K(+) current were not mimicked by either agonist. In a subgroup of FS interneurons, the slowly inactivating membrane outward rectification evoked by depolarizing voltage steps was also attenuated by DA. Collectively, these data showed that DA depolarizes FS interneurons by suppressing a voltage-independent 'leak' K(+) current (via D1/D5 receptor mechanism) and an inwardly rectifying K(+) current (via unknown DA mechanisms). Additional suppression of a slowly inactivating K(+) current led to increase in repetitive firing in response to depolarizing inputs. This D1-induced increase in interneuron excitability enhances GABAergic transmission to PFC pyramidal neurons and could represent a mechanism via which DA suppresses persistent firing of pyramidal neurons in vivo.

Action Potentials↗
PubMed2000

Specialisation within the prefrontal cortex: the ventral prefrontal cortex and associative learning.

This paper provides evidence that the ventral prefrontal cortex plays a role in the learning of tasks in which subjects must learn to associate visual cues and responses. Imaging with both positron-emission tomography (PET) and functional magnetic-resonance imaging (fMRI) reveals learning-related increases in activity when normal subjects learn visual associative tasks. Evidence is also presented from an event-related fMRI study that activity in this area is time-locked both to the presentation of the visual stimuli and also to the time of the motor response. Finally, it is shown in a study of monkeys that removal of the ventral prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a visual associative task (visual matching), even though there were no demands on working memory. It is, therefore, proposed that the ventral prefrontal cortex constitutes part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. On the basis of the existing anatomical and electrophysiological data, it is argued that the prefrontal cortex is the only area that can represent cues, responses and outcomes.

Animals↗
PubMed2005

ELISA methods to measure cholinergic markers and nerve growth factor receptors in cortex, hippocampus, prefrontal cortex, and basal forebrain from rat brain.

The central cholinergic system has a fundamental role in normal cognitive function, and in diseases that exhibit cognitive dysfunction. The purpose of this study was to design ELISA methods to measure proteins that have essential functions in the central cholinergic system. We were particularly interested in quantifying proteins that respond directly or indirectly to nerve growth factor (NGF). ELISAs offer advantages over Western blot analyses and other methods, such as increased sensitivity, decreased assay variability, increased efficiency, and decreased cost. We developed indirect ELISA methods for: choline acetyltransferase (ChAT); the vesicular acetylcholine transporter (VAChT); the high affinity choline transporter (HACT/CHT); TrkA, the high affinity NGF receptor; the p75 neurotrophin receptor (p75(NTR)). A sandwich ELISA was developed to measure tyrosine-phosphorylated TrkA in brain lysates. We used these ELISAs to compare levels of the above proteins in important memory-related brain regions--basal forebrain, hippocampus, cortex, and prefrontal cortex--from old and young rats. We identified age-related differences in the levels of the aforementioned proteins (e.g., VAChT and HACT/CHT in hippocampus). Thus, these ELISA methods should be particularly useful for comparing the effects of age, disease, drugs, and toxicants on brain levels of key cholinergic and growth factor-related proteins.

Acetylcholine↗
PubMed2001

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions.

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior.

Action Potentials↗
PubMed2003

Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate.

We used transneuronal transport of neurotropic viruses to examine the topographic organization of circuits linking the cerebellar cortex with the arm area of the primary motor cortex (M1) and with area 46 in dorsolateral prefrontal cortex of monkeys. Retrograde transneuronal transport of the CVS-11 (challenge virus strain 11) strain of rabies virus in cerebello-thalamocortical pathways revealed that the arm area of M1 receives input from Purkinje cells located primarily in lobules IV-VI of the cerebellar cortex. In contrast, transneuronal transport of rabies from area 46 revealed that it receives input from Purkinje cells located primarily in Crus II of the ansiform lobule. Thus, both M1 and area 46 are the targets of output from the cerebellar cortex. However, the output to each area of the cerebral cortex originates from Purkinje cells in different regions of the cerebellar cortex. Anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 (HSV1) revealed that neurons in the arm area of M1 project via the pons to granule cells primarily in lobules IV-VI, whereas neurons in area 46 project to granule cells primarily in Crus II. Together, the findings from rabies and HSV1 experiments indicate that the regions of the cerebellar cortex that receive input from M1 are the same as those that project to M1. Similarly, the regions of the cerebellar cortex that receive input from area 46 are the same as those that project to area 46. Thus, our observations suggest that multiple closed-loop circuits represent a fundamental architectural feature of cerebrocerebellar interactions.

Animals↗
PubMed2006

Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex.

Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding.

Animals↗
PubMed1992

Excitatory Amino Acid Pathway from the Hippocampus to the Prefrontal Cortex. Contribution of AMPA Receptors in Hippocampo-prefrontal Cortex Transmission.

Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde d-[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d-[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-d-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.

Journal Article↗
PubMed2002

Coding and monitoring of motivational context in the primate prefrontal cortex.

The prefrontal cortex is involved in acquiring and maintaining information about context, including the set of task instructions and/or the outcome of previous stimulus-response sequences. Most studies on context-dependent processing in the prefrontal cortex have been concerned with such executive functions, but the prefrontal cortex is also involved in motivational operations. We thus wished to determine whether primate prefrontal neurons show evidence of representing the motivational context learned by the monkey. We trained monkeys in a delayed reaction task in which an instruction cue indicated the presence or absence of reward. In random alternation with no reward, the same one of several different kinds of food and liquid rewards was delivered repeatedly in a block of approximately 50 trials, so that reward information would define the motivational context. In response to an instruction cue indicating absence of reward, we found that neurons in the lateral prefrontal cortex not only predicted the absence of reward but also represented more specifically which kind of reward would be omitted in a given trial. These neurons seem to code contextual information concerning which kind of reward may be delivered in following trials. We also found prefrontal neurons that showed tonic baseline activity that may be related to monitoring such motivational context. The different types of neurons were distributed differently along the dorsoventral extent of the lateral prefrontal cortex. Such operations in the prefrontal cortex may be important for the monkey to maximize reward or to modify behavioral strategies and thus may contribute to executive control.

Animals↗
PubMed1996

Prepulse inhibition and latent inhibition: the role of dopamine in the medial prefrontal cortex.

The prefrontal cortex has often been implicated in the pathophysiology of schizophrenia. Schizophrenic patients are known to suffer from certain information processing deficits, which can be detected, among others, in the prepulse inhibition and the latent inhibition paradigm. The present study was designed to investigate the role of dopamine receptors in the medial prefrontal cortex in prepulse inhibition and latent inhibition. The results show that the local application of the selective antagonist of the dopamine D1-like receptor family, SCH 39166, into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Likewise, the selective antagonist of the dopamine D2-like receptor family, sulpiride, injected into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Neither of these antagonists, however, influenced latent inhibition as measured with the conditioned taste aversion paradigm. These data further indicate that the neuronal substrates of latent inhibition and prepulse inhibition are clearly different. Since the prefrontal cortex is intimately related to subcortical dopamine, the possible differential involvement of subcortical dopaminergic terminal fields in prepulse inhibition and latent inhibition is discussed.

Animals↗
PubMed2000

Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex.

In prefrontal cortex, 5-hydroxytryptamine(2A) (5-HT(2A)) receptors have been linked to the action of hallucinogens and atypical antidepressant/antipsychotic drugs. Previously, we have shown in cortical layer V pyramidal cells that a nonselective metabotropic glutamate (mGlu) receptor agonist suppresses the induction of excitatory postsynaptic potentials/currents (EPSPs/EPSCs) via activation of 5-HT(2A) receptors. In this study, we tested the ability of the selective mGlu2/3 agonist (1S,2S,5R, 6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and the selective mGlu2/3 antagonist 2S-2-amino-2-(1S, 2S-2-carboxycycloprop-1-yl)-3(xanthy-9-yl)propanoic acid (LY341495) to modulate serotonin(5-HT)-induced EPSPs and electrically evoked EPSPs by using intracellular recording from layer V pyramidal cells in medial prefrontal cortex. The mGlu2/3 antagonist LY341495 increased the frequency and amplitude of 5-HT-induced EPSCs, suggesting a role for mGlu2/3 receptors in mediating the action of endogenous glutamate on autoreceptors. Conversely, the mGlu2/3 agonist LY354740 was highly effective and potent (EC(50) = 89 nM) in suppressing glutamate release induced by 5-HT(2A) receptor activation in the medial prefrontal cortex, probably via a presynaptic mechanism. The mGlu2/3 antagonist LY341495 potently blocked the suppressant effect of LY354740 on 5-HT-induced EPSCs as well as electrically evoked early EPSPs. Autoradiography with the radioligands [(3)H]LY354740 and [(125)I](+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane showsa striking overlap of the laminar distribution of mGlu2/3 and 5-HT(2A) receptors in the medial prefrontal cortex that is not apparent in other cortical regions. These findings suggest a close coupling between mGlu2/3 and 5-HT(2A) receptors in the prefrontal cortex that may be relevant for novel therapeutic approaches in the treatment of neuropsychiatric syndromes such as depression and schizophrenia.

Amino Acids↗
PubMed2003

Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection.

Inhibitory control and error detection are among the highest evolved human self-monitoring functions. Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success. Different brain regions in inferior, mesial, and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks. The widespread activation reflects the fact that the designs used so far have comeasured additional noninhibitory cognitive functions such as selective attention, response competition, decision making, target detection, and inhibition failure. Here we use rapid, mixed trial, event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions. The difficulty of the stop task, requiring withholding of a triggered motor response, was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials, failing on the other half. This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection. Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex. Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices, presumably reflecting an attention network for error detection.

Adult↗
PubMed2004

Cooperation of the anterior cingulate cortex and dorsolateral prefrontal cortex for attention shifting.

Attention shifting in the working memory system plays an important role in goal-oriented behavior, such as reading, reasoning, and driving, because it involves several cognitive processes. This study identified brain activity leading to individual differences in attention shifting for dual-task performance by using the group comparison approach. A large-scale pilot study was initially conducted to select suitable good and poor performers. The fMRI experiment consisted of a dual-task condition and two single-task conditions. Under the dual-task condition, participants verified the status of letters while concurrently retaining arrow orientations. The behavioral results indicated that accuracy in arrow recognition was better in the good performers than in the poor performers under the dual-task condition but not under the single-task condition. Dual-task performance showed a positive correlation with mean signal change in the right anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC). Structural equation modeling indicated that effective connectivity between the right ACC and right DLPFC was present in the good performers but not in the poor performers, although activations of the task-dependent posterior regions were modulated by the right ACC and right DLPFC. We conclude that individual differences in attention shifting heavily depend on the functional efficiency of the cingulo-prefrontal network.

Adult↗