Convergence of cortical and thalamic input to direct and indirect pathway medium spiny neurons in the striatum

Icnelia Huerta-Ocampo,Juan Mena-Segovia,J Paul Bolam

doi:10.1007/s00429-013-0601-z

Abstract

The major afferent innervation of the basal ganglia is derived from the cortex and the thalamus. These excitatory inputs mainly target the striatum where they innervate the principal type of striatal neuron, the medium-sized spiny neurons (MSNs), and are critical in the expression of basal ganglia function. The aim of this work was to test directly whether corticostriatal and thalamostriatal terminals make convergent synaptic contact with individual direct and indirect pathway MSNs. Individual MSNs were recorded in vivo and labelled by the juxtacellular method in the striatum of BAC transgenic mice in which green fluorescent protein reports the expression of dopamine D1 or D2 receptors. After recovery of the neurons, the tissue was immunolabelled for vesicular glutamate transporters type 1 and 2, as markers of cortical and thalamic terminals, respectively. Three of each class of MSNs were reconstructed in 3D and second-order dendrites selected for electron microscopic analysis. Our findings show that direct and indirect pathway MSNs, located in the matrix compartment of the striatum, receive convergent input from cortex and thalamus preferentially on their spines. There were no differences in the pattern of innervation of direct and indirect pathway MSNs, but the cortical input is more prominent in both and synaptic density is greater for direct pathway neurons. The 3D reconstructions revealed no morphological differences between direct and indirect MSNs. Overall, our findings demonstrate that direct and indirect pathway MSNs located in the matrix receive convergent cortical and thalamic input and suggest that both cortical and thalamic inputs are involved in the activation of MSNs.

Highlights

The major afferent innervation of the basal ganglia is derived from the cortex and the thalamus and is carried principally by the glutamatergic corticostriatal and the thalamostriatal pathways
Using BAC transgenic mice in which eGFP is expressed under the D1 or D2 dopamine receptor promoters (Gong et al 2003; Valjent et al 2009), we recently demonstrated that corticostriatal and thalamostriatal terminals make synaptic contact with direct and indirect pathway mediumsized spiny neurons (MSNs) to a similar degree and provided indirect evidence of convergence of cortical and thalamic terminals on individual MSNs (Doig et al 2010), observations that are consistent with electrophysiological analyses (Kocsis et al 1977; Vandermaelen and Kitai 1980; Ding et al 2008; Smeal et al 2008; Nanda et al 2009; Sciamanna et al 2012; Ellender et al 2013)
Even though the activity of MSNs was highly irregular, it tended to organise during the cortical UP states

Summary

Introduction

The major afferent innervation of the basal ganglia is derived from the cortex and the thalamus and is carried principally by the glutamatergic corticostriatal and the thalamostriatal pathways. The whole of the cortical mantle projects onto the striatum in a highly topographically organised manner providing motor and cognitive information, and imparting functionality onto the striatum. The thalamostriatal system, which mainly originates in the intralaminar nuclei and provides the basal ganglia with ascending sensory, attentional and salience information, is critical in the expression of basal ganglia function. Identified in the early studies of basal ganglia connectivity (Kemp and Powell 1971), the thalamostriatal system is often not considered in studies of basal ganglia organisation or function. Several lines of evidence indicate that the thalamostriatal system is likely to be as functionally important as the corticostriatal system in the expression of basal ganglia function

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