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.

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.

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.

Patterns of termination of cerebellar and basal ganglia efferents in the rat thalamus. Strictly segregated and partly overlapping projections.

There is a widely held view that the cerebellum and basal ganglia act via separate subcortical channels. In rodent, however, electrophysiological evidence suggests that the output of these two systems is partly sent to a common set of thalamic neurons. In this study, the pattern of thalamic innervations provided by the deep cerebellar nuclei, the entopeduncular nucleus, and the substantia nigra pars reticulata was reinvestigated in the rat using the anterograde tracers Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin. Although the results confirm the existence of some overlap in the cerebellar and basal ganglia projection fields, they also show that in such convergent areas the cerebellar innervation is modest and consists of sparsely distributed fibers of thin diameter that provide a few scattered terminal boutons. These observations are consistent with the view that, in rodent as in higher mammalian species, the cerebellum and the basal ganglia act mainly via distinct thalamo-cortical channels.

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.

Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus.

Besides the nigro-collicular pathway, the nigro-thalamic projection to the ventromedial thalamic nucleus represents another efferent system of the basal ganglia through which striatum can influence motor centers. Since the striato-nigrothalamic circuit is composed of two successive GABAergic inhibitory links and the SNR is tonically active, we tested that by inhibiting nigrothalamic cells, the striatum may exert a facilitatory influence on VM-thalamocortical cells. We show that a transitory block of SNR (substantia nigra pars reticulata) firing (induced by either intranigral application of GABA or by stimulating the inhibitory striato-nigral pathway), causes a perfectly time-locked increase of activity in a large number of VM cells projecting to motor cortex. Moreover, the striatally evoked excitation of VM-thalamocortical cells requires the functional integrity of the GABAergic striato-nigral link. We conclude that the double inhibitory striato-nigrothalamic pathway acts on VM-thalamocortical cells through a disinhibitory mechanism. The functional implication of such a mechanism is discussed.

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.

Connections from the basal ganglia to the thalamus.

Many data suggest that the basal gnaglia exerts an indirect influence onto the motor cortex through the thalamus which receives pallidal and nigral efferences. According to the anatomical data, the internal segment of globus pallidus projects to the VL-VA and CM of thalamus and the substantia nigra sends axons ending in the VL and VA with an intranuclear organization which did not overlap the pallidal terminations. The electrophysiological records in the VL-VA nucleus demonstrates that pallidal stimulation induces an inhibitory response, mainly on thalamic neurons, which does not receive cerebellar input. If spreading of excitation is avoided, nigral stimulation also induces an inhibition at the thalamic level. This inhibitory effect can be recorded on relay cells with cerebellar input and cortical output as well as on nonrelay cells. The electrophysiological results in the case of the striatopallidal and striatonigral projections are also briefly reported.