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J M Deniau

Publications and source records attributed to J M Deniau.

At least 19 recordsLinked to original sources

Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata.

The substantia nigra pars reticulata (SNR), a major output station of basal ganglia, receives information from the cerebral cortex through three main pathways, i.e. a direct inhibitory trans-striatal pathway, an indirect excitatory trans-striatal pathway that involves the pallidum and the subthalamus and a direct excitatory trans-subthalamic pathway. In order to determine how cortical information flow originating from functionally distinct cortical areas and processed through the trans-striatal and trans-subthalamic pathways is integrated within the SNR, the responses induced by electrical stimulation of prefrontal, motor and auditory cortex in SNR cells were analyzed in anesthetized rats. Further confirming that direct striato-nigral pathways related to these functionally distinct cortical areas are organized in parallel channels, stimulation of the prefrontal, motor and auditory cortex induced an inhibitory response on distinct subpopulations of SNR cells. Within a given channel, the direct trans-striatal and the trans-subthalamic pathways converge on a large number of nigral cells. In addition, the present study reveals that nigral cells receiving an inhibitory input from a given cortical area through the direct trans-striatal pathway can also receive an excitatory input from a functionally distinct cortical area through the trans-subthalamic pathways. Such a convergence mainly occurred between the direct striato-nigral pathway issued from the auditory cortex and the trans-subthalamic pathways issued from the motor cortex. These data reveal the existence of a converging influence of trans-subthalamic and direct striato-nigral pathways not only within but also across channels. Within a given cortico-basal ganglia channel, the trans-subthalamic pathways likely contribute to the temporal shaping of the striato-nigral inhibition and thus of the disinhibition of the related nigral target nuclei in the thalamus and mesencephalon. Across channels, the specific interactions between trans-subthalamic and direct striato-nigral pathways could contribute to prevent inhibition of subpopulations of nigral cells implicated in competing functions.

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Dendritic arborizations of the rat substantia nigra pars reticulata neurons: spatial organization and relation to the lamellar compartmentation of striato-nigral projections.

The cerebral cortex provides a major source of inputs to the basal ganglia. As has been well documented, the topography of corticostriatal projections subdivides the striatum into a mosaic of functionally distinct sectors. How information flow from these striatal sectors remains segregated or not within basal ganglia output nuclei has to be established. Electrophysiologically identified neurons of the rat substantia nigra pars reticulata were labeled by juxtacellular injection of Neurobiotin, and the spatial organization of their dendritic arborizations was analyzed in relation to the projection fields of individual striatal sectors. Thirty-nine nigral neurons located in the projection territory of the distinct striatal sensorimotor sectors were reconstructed. The data show that the dendritic arborizations of nigral neurons conform to the geometry of striato-nigral projections. Like striatal projections, the arborizations formed a series of curved laminas enveloping a dorsolaterally located core. Although dendritic fields of the neurons lying in the laminae were flat, those located in the core were spherical or cylindrical, thereby conforming to the shape of the striatal projection fields. This remarkable alignment between the dendritic arborizations of nigral neurons and the projection fields from individual striatal districts supports the concept of a parallel architecture of the striato-nigral circuits. However, pars reticulata neurons usually extend part of their dendrites within adjacent striatal projection fields, thereby ensuring a continuum between channels. The extension of the dendritic arborizations within the striatal projection fields suggests that nigral neurons integrate the information that is relevant for the completion of the specific motor behavior they control.

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Segregation and convergence of information flow through the cortico-subthalamic pathways.

Cortico-basal ganglia circuits are organized in parallel channels. Information flow from functionally distinct cortical areas remains segregated within the striatum and through its direct projections to basal ganglia output structures. Whether such a segregation is maintained in trans-subthalamic circuits is still questioned. The effects of electrical stimulation of prefrontal, motor, and auditory cortex were analyzed in the subthalamic nucleus as well as in the striatum of anesthetized rats. In the striatum, cells (n = 300) presenting an excitatory response to stimulation of these cortical areas were located in distinct striatal territories, and none of the cells responded to two cortical stimulation sites. In the subthalamic nucleus, both prefrontal and motor cortex stimulations induced early and late excitatory responses as a result of activation of the direct cortico-subthalamic pathway and of the indirect cortico-striato-pallido-subthalamic pathway, respectively. Stimulation of the auditory cortex, which does not send direct projection to the subthalamic nucleus, induced only late excitatory responses. Among the subthalamic responding cells (n = 441), a few received both prefrontal and motor cortex (n = 19) or prefrontal and auditory cortex (n = 10) excitatory inputs, whereas a larger number of cells were activated from both motor and auditory cortices (n = 48). The data indicate that the segregation of cortical information flow originating from prefrontal, motor, and auditory cortices that occurred in the striatum is only partly maintained in the subthalamic nucleus. It can be proposed that the existence of specific patterns of convergence of information flow from these functionally distinct cortical areas in the subthalamic nucleus allows interactions between parallel channels.

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Relationship between EEG potentials and intracellular activity of striatal and cortico-striatal neurons: an in vivo study under different anesthetics.

The functions of the basal ganglia are achieved through excitation of striatal output neurons (SONs) by converging cortical glutamergic afferents. We assessed the relationship between different patterns of activity in cortico-striatal (C-S) cells and the electrical behavior of SONs in vivo. Intracellular activities of rat C-S neurons in the orofacial motor cortex and of SONs, located in the projection field of this cortical region, were recorded under different anesthetics, which generate various temporal patterns of cortical activity. A surface electroencephalogram (EEG) of the orofacial motor cortex was simultaneously performed with intracellular recordings and EEG waves were used as correlates of a coherent synaptic activity in cortical neurons. Under barbiturate anesthesia C-S neurons showed rhythmic (5--7 Hz) supra-threshold depolarizations in phase with large amplitude EEG waves. The correlative activity of SONs was characterized by large amplitude oscillation-like synaptic depolarizations that could trigger action potentials. Under ketamine-xylazine anesthesia C-S neurons exhibited a step-like behavior consisting of depolarizing plateaus (up states), leading to multiple spike discharges, interrupted by hyperpolarizing periods (down states). The related activity of SONs was step-like membrane potential fluctuations with firing confined to the early part of the striatal up state. In C-S neurons and SONs up states coincided with slow recurrent EEG waves (approximately 1 Hz). Finally, under neurolept-analgesia an apparently disorganized EEG activity was associated with a lack of rhythmic discharge in C-S neurons. This uncorrelated activity in C-S neurons resulted in an absence of spontaneous firing as well as of large amplitude synaptic depolarizations in SONs. In the present study we demonstrate that SONs shape their input-output relationship by filtering out uncorrelated synaptic activity and that a minimal synchronization in the cortico-striatal afferents is required to produce significant synaptic depolarization in SONs.

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Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the cortico-nigral circuits.

The prelimbic/medial orbital areas (PL/MO) of the rat prefrontal cortex are connected to substantia nigra pars reticulata (SNR) through three main circuits: a direct nucleus accumbens (NAcc)-SNR pathway, an indirect NAcc-SNR pathway involving the ventral pallidum (VP) and the subthalamic nucleus (STN), and a disynaptic cortico-STN-SNR pathway. The present study was undertaken to characterize the effect of PL/MO stimulation on SNR cells and to determine the contribution of these different pathways. The major pattern of responses observed in the SNR was an inhibition preceded by an early excitation and followed or not by a late excitation. The inhibition resulted from the activation of the direct NAcc-SNR pathway because it disappeared after acute blockade of the glutamatergic cortico-striatal transmission by CNQX application into the NAcc. The late excitation resulted from the activation of the indirect NAcc-VP-STN-SNR pathway via a disinhibition of the STN because it disappeared after either CNQX application into the NAcc or blockade of the GABAergic striato-pallidal transmission by bicuculline application into the VP. The early excitation, which was markedly decreased after blockade of the cortico-STN transmission by CNQX application into the STN, resulted from the activation of the disynaptic cortico-STN-SNR pathway. Finally, the blockade of the cortico-STN-VP circuit by CNQX application into STN or VP modified the influence of the trans-striatal circuits on SNR cells. This study suggests that, in the prefrontal cortex-basal ganglia circuits, the trans-subthalamic pathways, by their excitatory effects, participate in the shaping of the inhibitory influence of the direct striato-nigral pathway on SNR neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

On the putative contribution of GABA(B) receptors to the electrical events occurring during spontaneous spike and wave discharges.

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of -68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that there are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA(B) IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.

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Three-dimensional distribution of nigrostriatal neurons in the rat: relation to the topography of striatonigral projections.

Functional regions of the rat striatum related to identified cortical territories were injected ionophoretically with wheat germ agglutinin coupled to horseradish peroxidase. Coronal serial sections were cut throughout the substantia nigra. The distributions of labelled striatal projections and nigrostriatal neurons were studied. Using software developed in our laboratory, three-dimensional reconstructions were calculated which confirmed and extended the organizational scheme of striatonigral projections already reported by our group. These projections were organized as a set of longitudinal lamellae spatially organized so as to segregate the flow of information emanating from striatal regions affiliated to sensorimotor and associative-limbic cortical areas. In addition, the relationship between the striatonigral projections and the nigrostriatal neurons was studied by three-dimensional reconstruction. For each striatal injection site, two populations of retrogradely labelled nigral neurons could be discriminated by their position with respect to the striatal projection field. The first one occupied a proximal position, in register with the labelled striatal projections, while the second was more distal. The populations of proximal neurons which innervate different functional striatal sectors were segregated both mediolaterally, dorsoventrally and rostrocaudally, while the populations of distal neurons were more scattered and showed a lesser degree of spatial segregation. The organization of these two populations with respect to the striatal projection fields suggests that the substantia nigra might control the flow of cortical information through the striatum via two different modalities, based respectively on a closed nigrostriatal loop involving the proximal neurons, and an open loop involving the distal ones.

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In vivo induction of striatal long-term potentiation by low-frequency stimulation of the cerebral cortex.

Both long-term depression and long-term potentiation have been described at corticostriatal synapses. These long-lasting changes in synaptic strength were classically induced by high-frequency (100 Hz) electrical stimulations of cortical afferents. The purpose of the present study was to test the ability of corticostriatal connections to express use-dependent modifications after cortical stimulation applied at the frequency of synchronization of corticostriatal inputs observed in our in vivo preparation, i.e. the barbiturate-anesthetized rat. For this study we used an identified monosynaptic corticostriatal pathway, between the orofacial motor cortex and its target region in the striatum. Intracellular recording of striatal output neurons showed spontaneous large-amplitude oscillation-like depolarizations exhibiting a strong periodicity with a narrow frequency band at 5 Hz. Using the focal electroencephalogram of the cortical region projecting to the recorded cells, we found that membrane potential oscillations in striatal neurons were in phase with episodes of spontaneous cortical spindle waves. To determine directly the pattern of activity of corticostriatal neurons, we performed intracellular recordings of electrophysiologically identified corticostriatal neurons simultaneously with the corresponding surface electroencephalogram. We found that corticostriatal cells (n = 7) exhibited periods of spontaneous 5-Hz discharges in phase with the cortical spindle waves. Therefore, we have tested the effect of repetitive cortical stimulations at this low frequency (5 Hz, 500-1000 pulses) on the corticostriatal synaptic efficacy. In 62% of cases (eight of 13 neurons tested), this conditioning was able to produce long-term potentiation in the corticostriatal synaptic efficacy. The mean increase of excitatory postsynaptic potential amplitude ranged from 13.3% to 172% (mean = 67.3%, n = 8). These results provide additional support for physiological long-term potentiation at corticostriatal connections. Furthermore, this study demonstrates that corticostriatal long-term potentiation can be induced by synchronization at low frequency of cortical afferents. Our data support the concept that the striatal output neuron may operate as a coincidence detector of converging cortical information.

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Effect of a functional impairment of corticostriatal transmission on cortically evoked expression of c-Fos and zif 268 in the rat basal ganglia.

The activity-dependent induction of immediate-early genes is commonly used to map activated neuronal networks. In a previous analysis of the cortico-basal ganglia circuits, we have shown that a cortical stimulation produces Fos protein expression in the striatum and the subthalamic nucleus, with a pattern which conforms to the anatomical organization of cortical projections [Sgambato V. et al. (1996) Neuroscience 81, 93-112]. In the present study, we examined the effects of a unilateral blockade of the corticostriatal transmission on c-fos and zif 268 messenger RNA expression evoked in the substantia nigra pars reticulata and the subthalamic nucleus following stimulation of the ipsilateral motor cortex. The blockade of the corticostriatal pathway was performed either by an excitotoxic striatal lesion or by an application of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione within the striatum. After application of the glutamate receptor antagonist, which prevented the cortical stimulation activating the GABAergic striatonigral pathway, the induction of both c-fos and zif 268 messenger RNAs was facilitated in the ipsilateral substantia nigra pars reticulata. In the subthalamic nucleus ipsilateral to the application of 6-cyano7-nitroquinoxaline-2,3-dione, the cellular discharges evoked by stimulation of the cortex were considerably shortened as a result of the blockade of the disinhibitory striato-pallido-subthalamic circuit. However, a strong expression of immediate-early genes was still induced by the cortical stimulation. By contrast, after unilateral kainate lesion of the striatum, the cortical stimulation was no longer able to induce c-fos and zif 268 messenger RNA expression in the ipsilateral subthalamic nucleus and in the substantia nigra pars reticulata bilaterally. The lack of immediate-early gene induction strongly contrasted with the neuronal discharges evoked in these nuclei by the cortical stimulation. Comparison between the cortically evoked neuronal activities and the pattern of immediate-early gene expression suggests that the induction of immediate-early genes in the basal ganglia mainly reflects the level of synaptic activity rather than the frequency of discharge of the postsynaptic neurons. Moreover, the results stress that modifications of immediate-early gene expression observed in the basal ganglia after an acute or a chronic interruption of the corticostriatal transmission are not superimposable.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits.

The prelimbic-medial orbital areas (PL/MO) of the prefrontal cortex are connected to the medial part of the subthalamic nucleus (STN) through a direct projection and an indirect circuit that involves the core of the nucleus accumbens (NAcc) and the ventral pallidum (VP). In the present study, the influence of the PL/MO on the discharge of STN cells has been characterized. The major pattern of the responses observed after stimulation of PL/MO consisted of two excitatory peaks often separated by a brief inhibitory period. The early excitation was most likely to be caused by the activation of direct cortical inputs because its latency matches the conduction time of the prefrontal STN projections. The late excitation resulted from the activation of the indirect PL/MO-STN pathway that operates through a disinhibitory process. Indeed, the late excitation was no longer observed after acute blockade of the glutamatergic corticostriatal transmission by CNQX application into the NAcc. A similar effect was obtained after the blockade of the GABAergic striatopallidal transmission by bicuculline application into the VP. Finally, the brief inhibition that followed the early excitation was likely to result from the activation of a feedback inhibitory loop through VP because this inhibition was no longer observed after the blockade of STN inputs by CNQX application into the VP. This study further indicates the implication of STN in prefrontal basal ganglia circuits and underlines that in addition to a direct excitatory input, medial STN receives an indirect excitatory influence from PL/MO through an NAcc-VP-STN disinhibitory circuit.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy.

1. In vivo extracellular and intracellular recordings were performed from thalamocortical (TC) neurones in a genetic model of absence epilepsy (genetic absence epilepsy rats from Strasbourg) during spontaneous spike and wave discharges (SWDs). 2. Extracellularly recorded single units (n = 14) fired either a single action potential or a high frequency burst of up to three action potentials, concomitantly with the spike component of the spike-wave complex. 3. Three main events characterized the intracellular activity of twenty-six out of twenty-eight TC neurones during SWDs: a small amplitude tonic hyperpolarization that was present throughout the SWD, rhythmic sequences of EPSP/IPSPs occurring concomitantly with the spike-wave complexes, and a small tonic depolarization at the end of the SWD. The rhythmic IPSPs, but not the tonic hyperpolarization, were mediated by activation of GABAA receptors since they reversed in polarity at -68 mV and appeared as depolarizing events when recording with KCl-filled electrodes. 4. The intracellular activity of the remaining two TC neurones consisted of rhythmic low threshold Ca2+ potentials, with a few EPSP/IPSP sequences present at the start of the SWD. 5. These results obtained in a well-established genetic model of absence epilepsy do not support the hypothesis that the intracellular activity of TC neurones during SWDs involves rhythmic sequences of GABAB IPSPs and low threshold Ca2+ potentials.

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Prefrontal cortex-basal ganglia circuits in the rat: involvement of ventral pallidum and subthalamic nucleus.

The core of the nucleus accumbens (NAcc core) is the principal input structure to the basal ganglia circuitry for the prelimbic and medial orbital areas (PL/MO) of the prefrontal cortex. As is now well recognized in the rat, the main basal ganglia output of this prefrontal channel is the dorsomedial part of the substantia nigra pars reticulata (SNR) and not the ventral pallidum as previously suggested. There is evidence suggesting that the ventral pallidum is rather involved with the subthalamic nucleus (STN) in an indirect NAcc-SNR pathway. Indeed, we have recently shown that the NAcc core sends an inhibitory input to the lateral ventral pallidum (VPl), which projects to the medial STN. In the present study, we injected biocytin into the medial STN, at a site where neurons presented an inhibitory response to VPl stimulation. This produced anterogradely labelled fibres in the medial SNR and in the VPl. Furthermore, the stimulation of the VPl induced an inhibition in a majority of the STN cells identified, by the antidromic activation method, as projecting to SNR (76.6%) and/or back to the VPl (72.7%). In conclusion, these data further demonstrate the existence of an indirect striato-nigral pathway in the PL/MO channel and indicate that VPl is involved in an inhibitory feedback circuit, which modulates the discharge of medial STN. These results indicate that the medial STN is implicated in the limbic/cognitive functions of the basal ganglia.

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In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation.

The purpose of the present study was to investigate in vivo the activity-dependent plasticity of glutamatergic cortico-striatal synapses. Electrical stimuli were applied in the facial motor cortex and intracellular recordings were performed in the ipsilateral striatal projection field of this cortical area. Recorded cells exhibited the typical intrinsic membrane properties of striatal output neurons and were identified morphologically as medium spiny type I neurons. Subthreshold cortical tetanization produced either short-term posttetanic potentiation or short-term depression of cortically-evoked excitatory postsynaptic potentials. When coupled with a postsynaptic depolarization leading the membrane potential to a suprathreshold level, the tetanus induced long-term potentiation (LTP) of cortico-striatal synaptic transmission. Induction of striatal LTP was prevented by intracellular injection of a calcium chelator suggesting that this synaptic plasticity involves an increase of postsynaptic free calcium concentration. Contrasting with previous in vitro studies our findings demonstrate that LTP constitutes the normal form of use-dependent plasticity at cortico-striatal synapses. Since excitation of striatal neurons produces a disinhibition of premotor networks, LTP at excitatory striatal inputs should favor the initiation of movements and therefore could be critical for the functions of basal ganglia in motor learning.

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Position of the ventral pallidum in the rat prefrontal cortex-basal ganglia circuit.

The ventral pallidum receives major inputs from the nucleus accumbens, a striatal region related to the prefrontal cortex. The ventral pallidum, through its projections to the mediodorsal nucleus of the thalamus, has been considered as the main output structure of the prefrontal-basal ganglia circuits. However, as shown recently, the ventral pallidum also sends efferents to the subthalamic nucleus and the substantia nigra, suggesting that it could participate in intrinsic basal ganglia circuits. The aim of the present investigation was to determine the position of the ventral pallidum in the prefrontal-basal ganglia circuit originating from the prelimbic and medial orbital areas. Following injections of biocytin (an anterograde tracer) into the region of the core of the nucleus accumbens receiving excitatory inputs from the prelimbic and medial orbital areas, axonal terminal fields were observed in a delineated dorsal region of the ventral pallidum. When the biocytin injections were made into this ventral pallidal region, anterogradely labelled fibres were observed in both the dorsomedial substantia nigra pars reticulata and the medial subthalamic nucleus, but not in the mediodorsal nucleus of the thalamus. Confirming these anatomical observations, electrical stimulation of the core of the nucleus accumbens induced an inhibition of the spontaneous activity (D=34.9+/-13.3 ms, L=9.2+/-3.3 ms) in 46.5% of the ventral pallidal cells. Among these responding cells, 43% were antidromically driven from the subthalamic nucleus, 30% from the substantia nigra pars reticulata and only 6% from the mediodorsal nucleus of the thalamus. These data demonstrate that the region of the ventral pallidum involved in the prefrontal cortex-basal ganglia circuit originating from the prelimbic and medial orbital areas represents essentially a ventral subcommissural extension of the external segment of the globus pallidus since it exhibits similar extrinsic connections and functional characteristics. In conclusion, in this prelimbic and medial orbital channel, the ventral pallidum cannot be considered as a major output structure but is essentially involved in intrinsic basal ganglia circuits.

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Effect of electrical stimulation of the cerebral cortex on the expression of the Fos protein in the basal ganglia.

The protein Fos is a transcription factor which is quickly induced in response to a variety of extracellular signals. Since this protein is expressed in a variety of neuronal systems in response to activation of synaptic afferents, it has been suggested that it might contribute to activity-dependent plasticity in neural networks. The present study investigated the effect of cortical electrical stimulation on the expression of Fos in the basal ganglia in the rat, a group of structures that participate in sensorimotor learning. Results show that the repetitive application of electrical shocks in restricted areas of the cerebral cortex induces an expression of Fos mostly confined to the striatum and the subthalamic nucleus. The induction which can be elicited from different cortical areas (sensorimotor, auditory and limbic areas) does not require particular temporal patterns of stimulation but rather depends on the total number of shocks delivered during a given period of time. Moreover, it appears to be rather independent of the number of spikes discharged by the activated cells. In the striatum, the distribution of immunoreactive neurons is precisely delineated and conforms to the known topographical organization of stimulated corticostriatal projections. As demonstrated using a variety of double labelling techniques (combination of the immunocytochemical detection of Fos with the autoradiography of mu opioid receptors, calbindin immunocytochemistry, in situ hybridization of preproenkephalin and preprotachykinin A messenger RNAs), striatal neurons which express Fos are mostly localized in the matrix compartment and concern equally enkephaline and substance P containing efferent neurons. In the subthalamic nucleus, Fos expression evoked by cortical stimulation is also confined to discrete regions of the nucleus, the localizations corresponding to the primary projection site of the stimulated cortical cells. These results indicate that in addition to its phasic synaptic influence on the basal ganglia, the cerebral cortex could exert a long-term effect on the functional state of this system via a genomic control. Since the basal ganglia are involved in sensorimotor learning and motor habit formation, it is tempting to speculate that the activity-dependent Fos induction at corticostriatal and subthalamic synapses may contribute to consolidate the functionality of the neuronal networks activated during the completion of given motor tasks.

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Prefrontal cortex inputs of the nucleus accumbens-nigro-thalamic circuit.

The functional organization of the cortico-nucleus accumbens-substantia nigra pars reticulata circuit was investigated in the rat using combined anatomical and electrophysiological approaches. The nucleus accumbens neurons which project to the substantia nigra pars reticulata are located in a circumscribed region of the core immediately adjacent and extending dorsally to the anterior commissure. As shown by retrograde and anterograde transports of wheatgerm agglutinin conjugated to horseradish peroxidase, the region of the nucleus accumbens related to the substantia nigra was found to receive bilateral inputs from restricted areas of the medial and lateral prefrontal cortex, i.e., prelimbic/medial orbital and dorsal agranular insular areas. The electrical stimulation of these medial and lateral prefrontal cortical areas induced excitatory responses in nucleus accumbens neurons projecting to the dorsomedial substantia nigra pars reticulata. Interestingly, an important proportion (61%) of the nucleus accumbens-nigral cells responding to the stimulation of the lateral prefrontal cortex were also excited by the stimulation of the medial prefrontal cortex, demonstrating the existence of a convergent influence of these cortical areas on single nucleus accumbens cells. Furthermore, the present data also show that the stimulation of the medial prefrontal cortex results in a powerful inhibition of the tonic firing of the substantia nigra pars reticulata neurons. In conclusion, this study reveals the existence of a functional link between the prefrontal cortex (prelimbic/medial orbital and agranular insular areas) and the nucleus accumbens neurons which innervate the dorsomedial region of the substantia nigra pars reticulata. Since the dorsomedial region of substantia nigra pars reticulata is known to project to subfields of the mediodorsal and ventromedial thalamic nuclei related to the prefrontal cortex, the present data further demonstrate the existence of a prefrontal-nucleus accumbens-thalamo-cortical circuit involving the substantia nigra pars reticulata.

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