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Results for “Prefrontal Cortex”

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PubMed1994

The induction of serotonin3-like receptor supersensitivity and dopamine receptor subsensitivity in the rat medial prefrontal cortex after the intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine: a microiontophoretic study.

This study examines the effect of intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine on serotonin1A, serotonin2 and serotonin3 receptors in the rat medial prefrontal cortex using in vivo extracellular single cell recording and iontophoresis. Iontophoresis of the serotonin1A, serotonin1C,2 and serotonin3 receptor agonists (+-)-8-hydroxy-(di-n-propyl)aminotetralin, (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and 2-methylserotonin, respectively, produces a current-dependent (5-80 nA) suppression of the basal firing rate of medial prefrontal cortical cells in sham- and 5,7-dihydroxytryptamine-lesioned rats. The suppression produced by 2-methylserotonin and serotonin was significantly greater in 5,7-dihydroxytryptamine-lesioned rats than in control rats. No significant difference in the spontaneous activity of medial prefrontal cortex cells was observed between experimental and control rats after iontophoresis of (+-)-8-hydroxy-(di-n-propyl)aminotetralin or (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. There was no significant difference between the groups regarding the response of medial prefrontal cortex cells to the iontophoresis of GABA, whereas the response of medial prefrontal cortex cells to the iontophoresis of dopamine was significantly attenuated in animals pretreated with 5,7-dihydroxytryptamine compared to controls. Our results indicate that 5,7-dihydroxytryptamine-induced denervation selectively enhances the sensitivity of serotonin3-like receptors in the medial prefrontal cortex, which could, at least partially, account for the serotonin denervation supersensitivity. Moreover, the finding that the response of medial prefrontal cortical cells to the iontophoresis of dopamine is attenuated in 5,7-dihydroxytryptamine pretreated rats is consistent with the view that the inhibitory action of dopamine in the medial prefrontal cortex is dependent upon serotonin tone.

5,7-Dihydroxytryptamine↗

PubMed1993

Cocaine-sensitive and -insensitive dopamine uptake in prefrontal cortex, nucleus accumbens and striatum.

Behavioral studies have indicated that the reinforcing effects of cocaine are dependent on inhibition of dopamine uptake in nucleus accumbens and prefrontal cortex. As it has been suggested that dopamine uptake and cocaine-inhibition of dopamine uptake may differ in nucleus accumbens, prefrontal cortex and striatum, we have further characterized dopamine uptake and its susceptibility to inhibition in these three regions. Dopamine uptake was resolved into two processes, which accounts for some of the apparent reported regional differences in sensitivity of dopamine to inhibition by cocaine. One, which is probably associated with uptake into dopaminergic terminals, was sensitive to 6-hydroxydopamine lesions, cocaine, GBR 12909 or ouabain and was dependent on temperature and sodium ion concentration; this was responsible for most of the observed uptake in tissue from striatum and nucleus accumbens, but not from prefrontal cortex. There appeared to be no regional difference in susceptibility of this mode of dopamine uptake to either cocaine or GBR 12909. The other type of dopamine uptake, which represented a significant proportion of the total in prefrontal cortex, but not in striatum or nucleus accumbens, was relatively insensitive to cocaine, GBR 12909 and ouabain and was dependent on temperature, but not sodium ion concentration. In addition, the cocaine-insensitive dopamine uptake was more sensitive to inhibition by dopamine than serotonin, but did not distinguish between dopamine and norepinephrine. The occurrence of cocaine-sensitive dopamine uptake in all examined regions and its equal sensitivity to cocaine and GBR 12909 is consistent with the involvement of nucleus accumbens and/or prefrontal cortex in the reinforcing effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed2005

Effects of the metabotropic glutamate receptor agonist, ACPD, on the extracellular concentrations of GABA and acetylcholine in the prefrontal cortex of the rat during the normal process of aging.

The aim of the present study was to investigate the effects of activation of metabotropic glutamate receptors (mGluR) on the extracellular concentrations of GABA and acetylcholine in the prefrontal cortex of freely moving rats of different groups of age. Perfusion, through the microdialysis probe, of the agonist of mGluR, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100, 500 and 1000 microM), in the prefrontal cortex of young rats produced a dose-related increase of the dialysate concentrations of GABA. The effects of perfusion of ACPD on the concentrations of GABA were attenuated in middle-aged rats. In the prefrontal cortex of aged rats, perfusion of ACPD produced no changes in dialysate concentrations of GABA at any of the doses used. Conversely, perfusion of ACPD (100, 500 and 1000 microM) in the prefrontal cortex of young, middle-aged and aged rats did not modify the dialysate concentrations of acetylcholine. Basal concentrations of acetylcholine in the prefrontal cortex of middle-aged and aged rats were significantly lower than those in young rats. In contrast, basal dialysate concentrations of GABA were not significantly different in young, middle-aged and aged rats. These results suggest that the interaction GABA-glutamate in the prefrontal cortex, mediated by mGluRs, changes with age.

Acetylcholine↗

PubMed1982

Organization of cortical afferents to the prefrontal cortex in the bush baby (Galago senegalensis).

Cortical afferents to the prefrontal cortex were studied in 10 bush babies (Galago senegalensis) by means of somatopetal transport of horseradish peroxidase. The lateral injections invariably labeled neurons in the temporal cortex and in most cases also in the insular and parietal regions. In some of these brains the cingulate and retrosplenial areas contained labeled perikarya. Injections into the medial cortex, on the other hand, consistently labeled cell bodies in the cingulate cortex, but not in the insular, temporal and parietal regions. When both lateral and medial sites of the bush baby's prefrontal cortex are considered together, apparently fewer cortical areas (as defined by Brodmann's cytoarchitectonic maps) project to the prefrontal cortex in the bush baby than in the rhesus monkey. This statement holds for both ipsi- and contralateral projections.

Afferent Pathways↗

PubMed1997

Areal segregation of face-processing neurons in prefrontal cortex.

A central issue in cognitive neuroscience concerns the functional architecture of the prefrontal cortex and the degree to which it is organized by sensory domain. To examine this issue, multiple areas of the macaque monkey prefrontal cortex were mapped for selective responses to visual stimuli that are prototypical of the brain's object vision pathway-pictorial representations of faces. Prefrontal neurons not only selectively process information related to the identity of faces but, importantly, such neurons are localized to a remarkably restricted area. These findings suggest that the prefrontal cortex is functionally compartmentalized with respect to the nature of its inputs.

Action Potentials↗

PubMed2001

Prefrontal cortex lesions augment the location-related firing properties of area TE/perirhinal cortex neurons in a working memory task.

It has previously been proposed that prefrontal cortex may have some role in keeping temporal cortex-based representations "on-line" during a working memory task. To test this hypothesis, the effects of electrolytic prefrontal cortex lesions on the firing of area TE and perirhinal cortex (PRC) neurons were examined while rats performed a delayed non-match to position task in the T-maze. The behavioural performance of control (n = 4) and lesioned (n = 4) animals were similar during this task, and many neurons displayed a statistically significant location-related variation in firing rate during the sample (44/56 neurons) and test (39/56 neurons) phases. Units from prefrontal-lesioned animals (82%) were more likely to display a significant variation in firing across the maze compared to controls (50%; P < 0.01), and to have more discrete location-related properties (50% of neurons) compared to the control (5%) group (P < 0.0005). This finding suggests that prefrontal cortex normally modulates the transmission and/or processing of spatial information in area TE/PRC during a working memory task. Modulation could be mediated through direct connections between the structures or via prefrontal control of subcortical structures. This finding has implications for our understanding of prefrontal-temporal involvement in memory and cognitive disorders.

Action Potentials↗

PubMed2004

NMDA receptor function in the prefrontal cortex of a rat model for attention-deficit hyperactivity disorder.

The spontaneously hypertensive rat (SHR) is an accepted model for attention-deficit hyperactivity disorder (ADHD) since it displays the major symptoms of ADHD (hyperactivity, impulsivity, and poor performance in tasks that require sustained attention). We have previously shown that glutamate activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors released significantly more norepinephrine from SHR prefrontal cortex slices than control Wistar-Kyoto (WKY) rats. The aim of this study was to determine whether N-methyl-D-aspartate (NMDA) receptor function is disturbed in the prefrontal cortex of SHR. Prefrontal cortex slices were incubated with 45Ca2+ in the presence or absence of 100 microM NMDA for 2 min. Activation of NMDA receptors stimulated significantly less Ca2+ uptake into prefrontal cortex slices of SHR than control WKY (2.8 +/- 0.17 vs. 3.7 +/- 0.38 nmol/mg protein, respectively, P < 0.05). Basal Ca2+ uptake into SHR slices was not significantly different from WKY. These findings are consistent with suggestions that the intracellular concentration of calcium is elevated and therefore the concentration gradient that drives calcium into the cell is decreased in SHR compared to WKY. Impaired NMDA receptor function in the prefrontal cortex of SHR could give rise to impaired cognition and an inability to sustain attention.

Animals↗

PubMed2005

Lateral prefrontal cortex: architectonic and functional organization.

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral-caudal axis and a dorsal-ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal-ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information.

Anatomy, Comparative↗

PubMed2007

Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward.

The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior.

Analysis of Variance↗

PubMed1997

Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD.

We examined the efficacy of several patterns of low-frequency stimulation for producing long-term depression (LTD) or depotentiation in the hippocampal fiber pathway to the prefrontal cortex in the anesthetized rat. Field potentials elicited by stimulation of the CA1/subicular region of the ventral hippocampus were recorded in the prelimbic area of the prefrontal cortex. We found no evidence that low-frequency trains (0.5-1 Hz), consisting of either single pulses, paired pulses (35-ms interpulse interval), or two-pulse bursts (5-ms interval), produce LTD in the prefrontal cortex. In contrast, all three stimulus protocols were found to induce a small-amplitude, persistent potentiation of the amplitude of the negative wave of the field response recorded in the prefrontal cortex. We also examined the ability of patterns of low-frequency stimulation to produce depotentiation of previously established long-term potentiation (LTP). Although low-frequency stimulation with single pulses or paired pulses was ineffective, we found that the two-pulse burst protocol selectively produced a rapid reversal of LTP in the hippocampo-prefrontal cortex pathway. Depotentiation is reversible and can be induced >2 h after the induction of LTP. Repeated trains failed to decrease the prefrontal cortex response below the original, unpotentiated level. These findings demonstrate the existence of a depotentiation mechanism that is capable of exerting powerful control over ongoing or recently induced synaptic plasticity in hippocampocortical connections in vivo.

Afferent Pathways↗

PubMed2000

Increased glutamate-stimulated norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have behavioral characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to the behavioral disturbances of children with attention-deficit hyperactivity disorder (ADHD). We have previously shown that dopaminergic and noradrenergic systems are disturbed in the prefrontal cortex of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. It was of interest to determine whether the underlying neural circuits that use glutamate as a neurotransmitter function normally in the prefrontal cortex of SHR. An in vitro superfusion technique was used to demonstrate that glutamate caused a concentration-dependent stimulation of [3H]norepinephrine release from rat prefrontal cortex slices. Glutamate (100 microM and 1 mM) caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from control slices. The effect of glutamate was not mediated by NMDA receptors, since NMDA (10 and 100 microM) did not exert any effect on norepinephrine release and MK-801 (10 microM) did not antagonize the effect of 100 microM glutamate. These results demonstrate that glutamate stimulates norepinephrine release from rat prefrontal cortex slices and that this increase is enhanced in SHR. The results are consistent with the suggestion that the noradrenergic system is overactive in prefrontal cortex of SHR, the animal model for ADHD.

Animals↗

PubMed1999

Cholinergic inputs to the rat medial prefrontal cortex mediate potentiation of the cardiovascular defensive response by the anxiogenic benzodiazephine receptor partial inverse agonist FG 7142.

Consistent with its putative anxiogenic actions, administration of the benzodiazepine receptor partial inverse agonist FG 7142 has been shown to potentiate defensive-like cardiovascular reactivity to an acoustic stimulus in the rat, an effect that appears to be mediated by the basal forebrain cholinergic system. The present studies tested the hypothesis that the basal forebrain cholinergic projections to the medial prefrontal cortex, an area that has been implicated in both anxiety and autonomic control, may be a relevant pathway underlying this response potentiation. Infusions of the muscarinic receptor agonist carbachol into the medial prefrontal cortex, but not into the lateral prefrontal cortex or the basolateral amygdala, mimicked the effects of systemically administered FG 7142 on the cardioacceleratory response. Infusions of the muscarinic antagonist atropine blocked this effect, as well as the response-potentiating actions of FG 7142. The effects of FG 7142 were also blocked by lesions of the cholinergic inputs to the medial prefrontal cortex produced by local infusions of the immunotoxin 192 immunoglobulin G-saporin into this area. These findings indicate that cholinergic activation of the medial prefrontal cortex is sufficient to enhance the cardioacceleratory defensive response, and that cholinergic inputs to the medial prefrontal cortex are necessary for the response-potentiating effects of FG 7142. These results are consistent with a recent neurobiological model of anxiety and autonomic control that attributes the enhanced processing of anxiety-related stimuli and contexts to increases in activity in cortical cholinergic inputs.

Animals↗

PubMed2001

Involvement of the dorsal anterior cingulate cortex in temporal behavioral sequencing: subregional analysis of the medial prefrontal cortex in rat.

We recently demonstrated that rats with dorsal anterior cingulate (ACd) cortical lesions were disrupted in the acquisition of a temporal Go/No-Go alternation task, suggesting either an involvement of this medial prefrontal subregion in sequencing temporally ordered behaviors or alternatively in more general response selection processes 'Gisquet-Verrier et al., Psychobiology 28 (2000) 248'. In the present study, the effects of ACd lesions were investigated in two different training situations. Both tasks involved response selection but only one of the two tasks required behavioral sequencing. In experiment 1, rats with ACd lesions were normally able to select Go and No-Go responses, when selection processes were based on a tone/light conditional rule that does not require temporal patterning. In experiment 2, ACd-lesioned rats were disrupted during the acquisition of a spatial alternation task that relies on temporal patterning. These results provide further evidence of ACd involvement in behavioral sequencing, regardless of the nature (spatial or non-spatial) of chained responses. A comparison of ACd lesions-induced effects with those obtained with lesions to the adjacent prelimbic-infralimbic area 'Delatour & Gisquet-Verrier, Behav. Neurosci. 110 (1996) 1282; Delatour & Gisquet-Verrier, Behav. Neurosci. 113 (1999) 941' reveals a double dissociation of these two regions that reflects a functional regionalization of the medial prefrontal cortex in the rat.

Animals↗

PubMed1989

An anterograde tracer study on the development of corticospinal projections from the medial prefrontal cortex in the rat.

The aim of the present study is to investigate, both qualitatively and quantitatively, the development of corticospinal (CS) projections from the medial prefrontal cortex of the rat. This study was carried out with the use of anterogradely transported wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) after iontophoretic injections in the medial prefrontal cortex. For comparison similar injections are made in the sensorimotor cortex. The CS axons of neurons situated in the medial prefrontal cortex have reached the first thoracic segment (T1) at postnatal day 3 (P3) and reach their most caudal extension in the spinal cord sixth thoracic segment (T6) at postnatal day 7 (P7) and then gradually disappear during the second postnatal week. Quantitative results revealed that after labelling of the medial prefrontal cortex no peaks in labelling density, neither at the cervical nor at the lumbar intumescence, were present. Furthermore, the CS axons of medial prefrontal neurons never showed any outgrowth into the spinal grey matter at any age studied. Concludingly, the extension and subsequent elimination of CS axons originating in the medial prefrontal cortex follow a similar time course as those from the occipital cortex (Dev. Brain Res., 36 (1987) 121-130).

Animals↗

PubMed1986

6-Hydroxydopamine and excitotoxin lesions of medial prefrontal cortex fail to affect schedule-induced drinking in the rat.

Schedule-induced drinking was examined in rats following 6-hydroxydopamine and N-methyl-D-aspartate lesions of the medial prefrontal cortex. 6-Hydroxydopamine reduced the concentrations of dopamine and noradrenaline in the medial prefrontal cortex to 17 and 37% of control values respectively, while changes were not observed in the nucleus accumbens. Lesions with N-methyl-D-aspartate were confined to the medial prefrontal cortex. Schedule-induced water consumption, determined over 11 consecutive 1 h/day testing sessions, was not significantly altered by either lesion. These results suggest that the mesocortical dopaminergic projection to the medial prefrontal cortex, and reciprocal projections from medial prefrontal cortex to the nucleus accumbens and the ventral tegmental area, are not essential for the acquisition of schedule-induced drinking.

Animals↗

PubMed1995

Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims.

Altered serotonin indices have been reported in the brain of suicide victims. We sought to localize the changes in presynaptic and postsynaptic serotonin receptors and identify an area of prefrontal cortex that may influence suicide risk. Quantitative autoradiography was performed in coronal sections of prefrontal cortex to determine whether serotonin 5-HT1A receptor (postsynaptic in cortex) and serotonin transporter (presynaptic) binding are different in suicide victims compared to matched controls. 5-HT1A receptor binding was higher in 85 of the 103 sampled areas in the suicide group (n = 18 pairs; P < 0.0001). The increase ranged from 17 to 30%. The increase was more pronounced in the ventrolateral prefrontal cortex. Serotonin transporter binding was found to be lower in the suicide group in all but one of the 43 sampled regions (n = 22 pairs; P < 0.0001). The reduction in binding was most pronounced in the ventrolateral prefrontal cortex, where the difference between suicides and controls ranged between 15 and 27%. Serotonin transporter and 5-HT1A binding were negatively correlated (r = -0.35 to -0.44, P = 0.04 to 0.007) within the same brain areas, suggesting common regulatory factors with opposite effects on binding to the two receptors. We conclude that suicide victims have an abnormality in the serotonin system involving predominantly the ventrolateral prefrontal cortex, and hypothesize that the serotonergic dysfunction in this brain region contributes to the risk for suicidal behavior.

Adult↗

PubMed1990

Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex: an electrophysiological study.

The neuromodulatory action of dopamine (DA) on acetylcholine (ACh)-evoked responses of prefrontal cortex (PFC) neurones were investigated electrophysiologically in rats anaesthetised with a combination of urethane and ketamine. Iontophoretic application of ACh-excited prefrontal cortex neurones. Concurrent application of DA (5-15 nA) resulted in complex changes in the ACh-evoked responses: (1) DA depressed spontaneous background discharges (designated as noise) proportionally more than the ACh-evoked discharges (designated as input signals), thus yielding an enhanced signal/noise ratio. This increase in signal/noise ratio by dopamine was reversed by iontophoretic application of the Da D2 antagonist sulpiride (20-50 nA). Nevertheless, iontophoretic application of D2 agonist quinpirole (5-35 nA) enhanced the ACh-evoked response, but was accompanied by some increase in spontaneous discharge, thus yielding no change in the signal/noise ratio. (2) DA also increased the signal/noise ratio by inducing a net increase of the ACh-evoked response but simultaneously suppressed the spontaneous activity of PFC neurones. This effect was more prominent following blockade of D1 receptors by SCH23390 (6 mg/kg, i.p.), suggesting that D1 receptors may normally inhibit D2 receptor function in the PFC. In addition, endogenous DA in the PFC did not play a significant part in modifying the ACh-evoked responses since the modulation of ACh-evoked response by DA or its D1 and D2 agonists was similar in both saline control and alpha-methyl-p-tyrosine-pretreated rats. (3) When ejected with larger iontophoretic current (16-35 nA), DA suppressed both the ACh-evoked and spontaneous discharge and this effect was mimicked by D1 agonist SKF38393 (5-15 nA). Taken together, these results suggest that complex dopaminergic modulation of the cholinergic responses of prefrontal cortex neurones are mediated by D1 and D2 receptors. This DA action may have a functional role in the cognitive-integrative processes occurring in the prefrontal cortex.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex.

Goal-directed actions are guided by expected outcomes of those actions. Humans with bilateral damage to ventromedial prefrontal cortex, or the amygdala, are deficient in their ability to use information about positive and negative outcomes to guide their choice behavior. Similarly, rats and monkeys with orbital prefrontal or amygdala damage have been found to be impaired in their responses to changing values of outcomes. In the present study, we tested whether direct, functional interaction between the amygdala and the orbital prefrontal cortex is necessary for guiding behavior based on expected outcomes. Unlike control monkeys, rhesus monkeys with surgical disconnection of these two structures, achieved by crossed unilateral lesions of the amygdala in one hemisphere and orbital prefrontal cortex in the other, combined with forebrain commissurotomy, were unable to adjust their choice behavior after a change in the outcome (here, a reduction in the value of a particular reinforcer). The lesions did not affect motivation to work for a food reinforcer, or food preferences, per se. Hence, the amygdala and orbital prefrontal cortex act as part of an integrated neural system guiding decision-making and adaptive response selection.

Accommodation, Ocular↗