Synaptic Convergence of Motor and Somatosensory Cortical Afferents onto GABAergic Interneurons in the Rat Striatum

Abstract

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

“…Although we lack a detailed anatomical understanding of the excitatory inputs to FSIs, such idiosyncratic firing seems to reflect unique sets of cortical inputs from the cortex (Ramanathan et al, 2002). Recently, a more coordinated increase in FSI activity has been observed specifically around the moment of choice execution in an operant action-selection task, and this was accompanied by an overall decrease in GP activity .…”

The Reward Circuit: Linking Primate Anatomy and Human Imaging

“…Here, axons from each area synapse onto single fast spiking GABAergic interneurons. Interestingly, these interneurons are more responsive to cortical input than the medium spiny cells (Charpier et al, 1999;Mallet et al, 2005;Ramanathan et al, 2002;Takada et al, 1998). This suggests a potentially critical role for interneurons to integrate information from different cortical areas before passing that information onto the medium spiny projection cells.…”

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

“…When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function.…”

“…striatum | optogenetics | beta oscillations | coherence | cholinergic interneurons E xaggerated beta oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1)(2)(3)(4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4,5).…”