Whole-Brain Mapping of Inputs to Projection Neurons and Cholinergic Interneurons in the Dorsal Striatum

Abstract

The dorsal striatum integrates inputs from multiple brain areas to coordinate voluntary movements, associative plasticity, and reinforcement learning. Its projection neurons consist of the GABAergic medium spiny neurons (MSNs) that express dopamine receptor type 1 (D1) or dopamine receptor type 2 (D2). Cholinergic interneurons account for a small portion of striatal neuron populations, but they play important roles in striatal functions by synapsing onto the MSNs and other local interneurons. By combining the modified rabies virus with specific Cre- mouse lines, a recent study mapped the monosynaptic input patterns to MSNs. Because only a small number of extrastriatal neurons were labeled in the prior study, it is important to reexamine the input patterns of MSNs with higher labeling efficiency. Additionally, the whole-brain innervation pattern of cholinergic interneurons remains unknown. Using the rabies virus-based transsynaptic tracing method in this study, we comprehensively charted the brain areas that provide direct inputs to D1-MSNs, D2-MSNs, and cholinergic interneurons in the dorsal striatum. We found that both types of projection neurons and the cholinergic interneurons receive extensive inputs from discrete brain areas in the cortex, thalamus, amygdala, and other subcortical areas, several of which were not reported in the previous study. The MSNs and cholinergic interneurons share largely common inputs from areas outside the striatum. However, innervations within the dorsal striatum represent a significantly larger proportion of total inputs for cholinergic interneurons than for the MSNs. The comprehensive maps of direct inputs to striatal MSNs and cholinergic interneurons shall assist future functional dissection of the striatal circuits.

An interactive framework for whole-brain maps at cellular resolution

“…Unlike previous studies that have relied on a small number of cortical neurons 34,35 , we quantified a large number of presynaptic neurons in the corticostriatal pathway (320055 neurons) after monosynaptic rabies tracing from distinct striatal subtypes. We analyzed the laminar distribution of the cell type-specific corticostriatal inputs in SSp and we found the major inputs to D1+ and D2+ striatal neurons were found in layer V, although we also found layer II/III and IV inputs (Fig.…”

Communication in Neural Circuits: Tools, Opportunities, and Challenges

“…Rabies viruses can also be further engineered to refine the starter-cell population (and hence the ODEs synapsing onto the starter-cell population) by pseudotyping with the coat protein EnvA, which causes infection to depend on TVA (avian tumor virus receptor), an avian receptor not found in the mammalian brain. Exogenous TVA in turn can be selectively expressed in the desired starter-cell subpopulation, such as midbrain dopamine neurons (Ogawa et al, 2014; Watabe-Uchida et al, 2012), serotonin neurons (Ogawa et al, 2014; Pollak Dorocic et al, 2014; Weissbourd et al, 2014), director indirect-pathway striatal projection neurons (Wall et al, 2013), and striatal cholinergic interneurons (Guo et al, 2015). …”

Striatal synapses, circuits, and Parkinson's disease

“…SPNs receive extra-striatal synaptic inputs from diverse brain areas, but the majority of their inputs are glutamatergic and arise from cortical and thalamic regions [11,12]. The strength of corticostriatal inputs, as well as how responsive SPNs are to these inputs, is under control of DA: D1R activation increases intrinsic excitability and promotes synaptic potentiation, while D2R activation decreases intrinsic excitability and promotes synaptic depression [1].…”

“…The growing consensus is that thalamostriatal inputs are highly heterogeneous in anatomical organizations, synaptic properties, and behavioral functions [75]. For example, the striatum receives glutamatergic afferents from a variety of thalamic nuclei [11,12], the best characterized of which is the parafascicular thalamic nuclei (PF) in rodents (or center median/ PF nuclei in primates) [76]. Non-PF thalamic projections make synaptic contacts mostly on dendritic spines of SPNs (‘axospinous’) like the corticostriatal inputs, but PF axons largely synapse on dendritic shafts (‘axoshaft’).…”