Cortical and Thalamic Innervation of Direct and Indirect Pathway Medium-Sized Spiny Neurons in Mouse Striatum

Abstract

The striatum receives major excitatory inputs from the cortex and thalamus that predominantly target the spines of medium-sized spiny neurons (MSNs). We aimed to determine whether there is any selectivity of these two excitatory afferents in their innervation of direct and indirect pathway MSNs. To address this, we used bacterial artificial chromosome transgenic mice, in which enhanced green fluorescent protein (EGFP) reports the presence of D 1 or D 2 dopamine receptor subtypes, markers of direct and indirect pathway MSNs, respectively. Excitatory afferents were identified by the selective expression of vesicular glutamate transporter type 1 (VGluT1) by corticostriatal afferents and vesicular glutamate transporter type 2 (VGluT2) by thalamostriatal afferents. A quantitative electron microscopic analysis was performed on striatal tissue from D 1 and D 2 mice that was double immunolabeled to reveal the EGFP and VGluT1 or VGluT2. We found that the proportion of synapses formed by terminals derived from the cortex and thalamus was similar for both direct and indirect pathway MSNs. Furthermore, qualitative analysis revealed that individual cortical or thalamic terminals form synapses with both direct and indirect pathway MSNs. Similarly, we observed a convergence of cortical and thalamic inputs onto individual MSNs of both direct and indirect pathway: individual EGFP-positive structures received input from both VGluT2-positive and VGluT2-negative terminals. These findings demonstrate that direct and indirect pathway MSNs are similarly innervated by cortical and thalamic afferents; both projections are thus likely to be critical in the control of MSNs and hence play fundamental roles in the expression of basal ganglia function.

Inhibitory Synapse Formation in a Co-culture Model Incorporating GABAergic Medium Spiny Neurons and HEK293 Cells Stably Expressing GABA_A Receptors

“…Therefore they lack the appropriate connections, inputs and secreted molecules from other cells that may influence the initial stages of synapse development. For example, in vivo medium spiny neurons are densely innervated by glutamatergic inputs from the cortex, thalamus and other brain regions 34 , however, in our neuronal cultures glutamatergic synapses do not form because these inputs are damaged during dissection of the striatal tissue. How the absence of functional glutamatergic synapses in cultured medium spiny neurons affects their ability to form GABAergic synapses with each other and/or HEK293 cells expressing GABA A Rs remains an open question.…”

Mouse Intracerebral Hemorrhage Models Produce Different Degrees of Initial and Delayed Damage, Axonal Sprouting, and Recovery

“…Both lesions targeted the dorsolateral striatum, the site of sensorimotor system function. 20,21 However, although these lesions overlap across animals in their location within the dorsolateral striatum of the mouse, their precise anatomic positions were not matched.…”

“…19 It is also a site of termination of axonal projections from cortex and a passage point where cortical projections pass through to thalamus, brainstem, and spinal cord. 20,21 Intracranial hemorrhage damages these connections. 22 The degree of loss of cortical projections to or through the striatum was measured by back-labeling all of the cortical axons that project to the site of the ICH with the axonal tracer CTb, within the collagenase or blood injection, and then measuring the retrogradely labeled cell bodies.…”

Temporal Convergence of Dynamic Cell Assemblies in the Striato-Pallidal Network

“…The thalamostriatal synapses have not been studied as extensively as the corticostriatal synapses although they constitute ϳ40 -50% of the glutamatergic synapses formed on MSN dendrites Doig et al, 2010). Physiologically, these two pathways are presumed to have different functional roles.…”