Travel-associated and autochthonous Zika virus infection in mainland France, 1 January to 15 July 2016.

During summer 2016, all the conditions for local mosquito-borne transmission of Zika virus (ZIKV) are met in mainland France: a competent vector, Aedes albopictus, a large number of travellers returning from ZIKV-affected areas, and an immunologically naive population. From 1 January to 15 July 2016, 625 persons with evidence of recent ZIKV infection were reported in mainland France. We describe the surveillance system in place and control measures implemented to reduce the risk of infection.

Autochthonous case of dengue in France, October 2013.

In October 2013, autochthonous dengue fever was diagnosed in a laboratory technician in Bouches-du-Rhone, southern France, a department colonised by Aedes albopictus since 2010. After ruling out occupational contamination, we identified the likely chain of local vector-borne transmission from which the autochthonous case arose. Though limited, this second occurrence of autochthonous dengue transmission in France highlights that efforts should be continued to rapidly detect dengue virus introduction and prevent its further dissemination in France.

First cases of Omicron in France are exhibiting mild symptoms, November 2021-January 2022.

OBJECTIVES: We aimed to investigate the first Omicron cases detected in France in order to assess case characteristics and provide supporting information on the possible impact of this variant on the healthcare system. METHODS: A standardized questionnaire was used to collect information from confirmed and probable Omicron cases. RESULTS: Median age of 468 investigated cases was 35 years, 376 were symptomatic (89%); 64% were vaccinated with two doses and 7% had received three doses. Loss of smell and taste were reported by 8.3% and 9% of cases, respectively. Seven cases were hospitalized, three of those were unvaccinated (including two with reported precondition). No admissions to intensive care and no deaths were reported. CONCLUSIONS: Our results confirm a mild clinical presentation among the first Omicron cases detected in France and highlight the importance for the national COVID-19 surveillance system to quickly detect and adapt to the emergence of a new variant.

Dopamine modulates temporal dynamics of feedforward inhibition in rat prefrontal cortex in vivo.

Midbrain dopamine (DA) neurons project to pyramidal cells and interneurons of the prefrontal cortex (PFC). At the microcircuit level, interneurons gate inputs to a network and regulate/pattern its outputs. Whereas several in vitro studies have examined the role of DA on PFC interneurons, few in vivo data are available. In this study, we show that DA influences the timing of interneuron firing. In particular, DA had a reductive influence on interneuron spontaneous firing, which in the context of the excitatory response of interneurons to hippocampal electrical stimulation, lead to a temporal focalization of the interneuron response. This suggests that the reductive influence of DA on interneuron excitability is responsible for filtering out weak excitatory inputs. The increase in the temporal precision of interneuron firing is a mechanism by which DA can modulate the temporal dynamics of feedforward inhibition in PFC circuits and can thereby influence cognitive information processing.

The pars reticulata of the substantia nigra: a window to basal ganglia output.

Together with the internal segment of the globus pallidus (GP(i)), the pars reticulata of the substantia nigra (SNr) provides a main output nucleus of the basal ganglia (BG) where the final stage of information processing within this system takes place. In the last decade, progress on the anatomical organization and functional properties of BG output neurons have shed some light on the mechanisms of integration taking place in these nuclei and leading to normal and pathological BG outflow. In this review focused on the SNr, after describing how the anatomical arrangement of nigral cells and their afferents determines specific input-output registers, we examine how the basic electrophysiological properties of the cells and their interaction with synaptic inputs contribute to the spatio-temporal shaping of BG output. The reported data show that the intrinsic membrane properties of the neurons subserves a tonic discharge allowing BG to gate the transmission of information to motor and cognitive systems thereby contributing to appropriate selection of behavior.

Disinhibition as a basic process in the expression of striatal functions.

During the past decade, electrophysiological approaches have greatly improved understanding of the involvement of the basal ganglia in motor behaviour. This review reports that the basal ganglia contribute to the initiation of movement by arousing executive motor centres via a disinhibitory mechanism. We propose that the basal ganglia output is used as a movement template specifying the motor elements to be engaged in directing movement in space.

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.

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.

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.

Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens.

The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.

Morphology of the substantia nigra pars reticulata projection neurons intracellularly labeled with HRP.

The technique of intracellular recording and staining of the same neuron with horseradish peroxidase (HRP) was used to study the soma-dendritic and axonal morphology of nigrothalamic and nigrotectal cells in the rats. The nigrothalamic and nigrotectal cells were spread throughout the dorsoventral extent of the pars reticulata (SNR) and exhibited the same soma-dendritic and axonal features. Both populations consisted of medium-sized and large cells with extensive dendritic fields overlapping in all three directions. Their axons collateralized within the substantia nigra (SN) and in the mesencephalic tegmentum. The intrinsic collaterals were thin and branched partly within the dendritic field of a parent cell partly in remote regions of the SNR, and even in the pars compacta (SNC). The extrinsic branches involved thin arborizations in the rostroventral mesencephalic reticular substance and thicker descending and ascending collaterals. This material was supplemented by physiologically nonidentified HRP stained medium-sized and large neurons located in the SNR. The two kinds displayed the same extent and orientation of their dendrites but the branching patterns differed slightly. Proximal dendrites of all cells were coarse and smooth; thinner distal dendrites had varicosities and spinelike appendages. Some dendrites, specially those near the crus cerebri, terminated in dendritic thickets bearing many pleomorphic appendages. The orientation of dendritic fields varied with dorsoventral position of cells within the SNR. The most ventral region of the SNR contained neurons with dendrites oriented parallel to the crus cerebri and thus remained confined to the deepest stratum. The dendrites of cells in the central region of SNR were oriented mainly anteroposteriorly and ventrally, the ventral dendrites terminating in the ventralmost layer. Cells in the dorsolateral part of the SNR were characterized by the large dorsoventral extent of their dendrites which penetrated the entire thickness of SN. This variation in the arrangement of dendritic fields indicates that the SN is organized in three dorsoventral layers.

Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease.

Elevated iron levels in the substantia nigra (SN) of the brain in Parkinson's disease (PD) may mediate lipid peroxidative reactions, promoting SN neuronal death. To assess SN iron accumulation in living PD patients and its relation to motor performance, we measured, in 13 nondemented PD patients and 10 normal control subjects, simple reaction time (SRT) and simple movement time (SMT), followed by head MRI in a 3-tesla system. We measured T2 and T2* in the right and left SN of all subjects and calculated R2', the relaxation rate due to local magnetic field in-homogeneities, from these values. Asymmetries of 1/T2 (R2), 1/T2* (R2*), or R2' versus asymmetries of SRT and SMT were assessed in eight PD subjects who had not taken anti-PD medication(s) for 12 hours. The average of right and left SN values for R2 was lower, and R2* and R2' were higher, in PD patients than in controls (R2, p = 0.046; R2*, p = 0.001; R2', p < 0.001). R2' best predicted group differences. The asymmetry of SRT performance was highly correlated with asymmetries of SN R2* (0.91; p = 0.001) and R2' (0.72; p = 0.03). These results strongly suggest that the increases in iron levels seen postmortem in the SN in PD are reflected in increased iron-related MRI contrast at 3 tesla in living PD patients. Correlations with motor performance in PD suggest that the clinical severity of PD may be related to SN iron accumulation.

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.

The lamellar organization of the rat substantia nigra pars reticulata: distribution of projection neurons.

As a major output station of the basal ganglia, the pars reticulata of the substantia nigra has stimulated much interest. In the past two decades there has been a growing body of evidence for a partition of this structure into separate channels to express the striatal processing. To further our knowledge on the functional partitioning of the rodent substantia nigra pars reticulata, the regional distribution of the nigral efferent cell groups that provide innervation of thalamus, colliculus and tegmentum has been detailed in rat using the wheatgerm agglutinin conjugated with horseradish peroxidase as an axonal tracer. To ensure a total visualization of the nigral efferent neurons we have, in a preliminary study, determined the total extent of the nigral terminal field in each of the nigral target structures using the anterograde transport of wheatgerm agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin. At variance with the classical view that nigral cells innervating distinct target structures form functionally distinct subnuclei, the results suggest a nigral compartmentation that rather relies upon specific associations of efferent cell groups. As disclosed, these associations are specified by topographic rules and spatially ordered in a series of curved laminae enveloping an excentrated dorsolateral core. In this onion-like model of the substantia nigra pars reticulata, each lamella defines an associative unit composed of a set of neurons innervating particular loci of thalamus, colliculus and/or tegmentum. This lamellar partitioning bestows the ability upon the substantia nigra to dispatch the striatal outflow via parallel and divergent channels to functionally associated target areas in thalamus and brainstem.

Spatio-temporal organization of a branched tecto-spinal/tecto-diencephalic neuronal system.

The aim of the present study was to identify in the rat the diencephalic nuclei addressed by ascending collaterals of tecto-spinal neurons. For this purpose we made use of anterograde axonal transport method to determine the pattern of diencephalic projections arising from the lateral portion of the superior colliculus where most of tecto-spinal neurons are lying. Next, we used the antidromic activation method to analyse whether some of these colliculo-diencephalic projections were provided through collaterals of tecto-spinal neurons. Following injections of wheatgerm agglutinin, conjugated with horseradish peroxidase, in the lateral part of the superior colliculus, anterograde labelling was observed in: the contralateral superior colliculus, the ipsilateral pretectal nuclei, subthalamic area (zona incerta and Forel field) and thalamic structures namely: dorsal and ventral lateral geniculate, parafascicular, posterior nuclear group, reuniens nuclei and lateral portion of medio-dorsal nucleus. Moreover, bilateral projections were revealed in the following thalamic nuclei: lateral posterior, ventro-medial, paracentral and central-lateral. In the electrophysiological study we established that the thalamic nuclei medio-dorsal/central-lateral, paracentral, ventral-medial and the zona incerta receive ascending collaterals of the tecto-spinal neurons. In addition, an axonal branch to the contralateral superior colliculus was also revealed. The various ascending and descending collaterals of each branched neuron exhibited a similar conduction time for action potentials. It is thus likely that the tecto-spinal/tecto-diencephalic neurons provide a synchronized influence on their targets. The functional implication of such a branched collicular efferent pathway is discussed. Considering that tecto-spinal neurons are one of the collicular neuronal populations on which the substantia nigra exerts its influence, new perspectives in the analysis of basal ganglia collicular relationships are given.

The lamellar organization of the rat substantia nigra pars reticulata: segregated patterns of striatal afferents and relationship to the topography of corticostriatal projections.

The striatonigral pathway provides one of the most direct routes for information flow through the basal ganglia system. Via this pathway information from sensory, motor and associative areas of the cerebral cortex are routed to a variety of thalamocortical and brainstem networks involved in the organization of motor behaviour. In a previous analysis of the rat substantia nigra pars reticulata we have shown that the nigral cells which project to thalamus, tectum and tegmentum are topographically ordered along a series of curved laminae. Extending these observations, the present study examined how striatal regions related to particular areas of the cerebral cortex innervate the lamellar keyboard of nigral output neurons. For this purpose, small microiontophoretic injections of wheat germ agglutinin conjugated to horseradish peroxidase were performed in the striatum and the distribution of retrogradely-labelled cells in the cerebral cortex and anterogradely-labelled axons in the substantia nigra were conjointly examined. The results indicate that with the exception of the striatal region related to the allocortex, all the various components of the striatal functional mosaic are represented in the substantia nigra pars reticulata. This representation is organized under the form of longitudinal bands which compose a series of curved laminae enveloping a core located dorsolaterally in the substantia nigra. The striatal mapping in substantia nigra pars reticulata is such that the projections of the auditory and visual compartments are confined to the most ventral lamina. More dorsally, an ordered representation of the body is achieved by the nigral lamination. The oral and perioral body parts are centred on the dorsolateral core and the more distal parts of the face and limbs are progressively set out in more peripheral laminae. In the region affiliated to the prefrontal cortex, the dorsal cingulate district innervate a ventromedial lamina, the prelimbic/insular district lie dorsal to it. Projections from lateral orbital and insular compartments extend laterally along the dorsal margin of the pars reticulata. Since the "onion-like" distribution of striatal inputs is precisely the form observed in the distribution of nigral efferent neurons, the present observations favour the view that the nigral lamination underlies formation of specific input-output channels of processing. Evidence is considered that these channels are specialized for particular classes of movements or behaviours and integrate the various information relevant to the completion of these movements or behaviours.

Indirect nucleus accumbens input to the prefrontal cortex via the substantia nigra pars reticulata: a combined anatomical and electrophysiological study in the rat.

The nucleus accumbens is a major component of the ventral striatum through which most of the limbic affiliated cortical areas gain access to the basal ganglia circuitry. In this study, the organization of the pathways linking the nucleus accumbens to the thalamus, via the substantia nigra pars reticulata, was examined in the rat using anatomical and electrophysiological methods. Use of anterograde and retrograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase has established that the core of the nucleus accumbens innervates a dorsal region of the substantia nigra pars reticulata which projects to subfields of the mediodorsal and ventral medial thalamic nuclei. These subfields consist of the rostral pole of the mediodorsal nucleus with the exception of its central segment and a region of the ventral medial nucleus, medial to the mammillothalamic tract. Confirming the existence of a nucleus accumbens nigrothalamic link, we have observed that electrical or chemical stimulation of the nucleus accumbens induces an inhibition of the spontaneous discharges of the nigral cells which project to the mediodorsal and ventral medial thalamic nuclei. Finally, the cortical projections of the thalamic subfields involved in the nucleus accumbens nigrothalamic circuit were determined using the anterograde and retrograde axonal transport of wheatgerm agglutinin conjugated with horseradish peroxidase. These subfields innervate mainly the prelimbic and to a lesser degree the orbital areas of the prefrontal cortex. The present data show that the substantia nigra pars reticulata is a major link between the core of the nucleus accumbens and the prefrontal cortex and provide further evidence for the concept of a parallel architecture in the basal ganglia thalamocortical circuits of the ventral striatum.

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.

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.

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.