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

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.

Sex differences in myelin-associated protein levels within and density of projections between the orbital frontal cortex and dorsal striatum of adult rats: Implications for inhibitory control

“…The excitatory glutamatergic projections from the OFC to dSTR are strongly implicated in impulse control (for review see, Eagle and Baunez, 2010). Studies using the vesicular glutamate transporter type 1 as a marker of cortical innervation indicate that dSTR medium-sized spiny neurons of both the direct and indirect pathway receive cortical input (Doig et al, 2010;Huerta-Ocampo et al, 2014). The balance between the direct and indirect pathways of the dSTR allows for the release of desired behavioral patterns while inhibiting undesired behavioral patterns (Miller and Buschman, 2007).…”

Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum

“…First, MOPr-mediated depression may selectively occur at thalamostriatal inputs, and the mixed population of inputs activated by electrical stimulation, including a subset of the thalamostriatal inputs recruited by optogenetic activation, may exhibit a kinetically different form of MOPr-mediated depression. We could speculate that electrical stimulation preferentially activates cortical inputs, given our placement of the stimulating electrode at the border of the dorsal striatum and overlying white matter and the predominant innervation of MSNs by cortical versus thalamic inputs 40 . Alternatively, electrical stimulation may activate unidentified, presumably non-motor cortical, inputs that display mOP-LTD independent of the MOPr-mediated depression observed at thalamostriatal inputs.…”

Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults

“…This region heavily connects to the striatum and other parts of the basal ganglia (McFarland and Haber, 2002). Specifically, these excitatory inputs from the thalamus mainly target the striatum, where they innervate the principal type of striatal neuron and are critical in the expression of basal ganglia function (Huerta-Ocampo et al, 2014). In schizophrenia patients, high levels of DA have been reported in the thalamus (Oke et al, 1988), and since then it has been discussed whether this area is critical to the pathophysiology of schizophrenia (Moghaddam, 2010).…”