Summary: Researchers are characterizing a new neuronal population in the striatum that appears to be responsible for the interaction between acetylcholine and GABA.
Source: Karolinska Institute
A new study from the Department of Neurosciences at the Karolinska Institutet characterizes a new neuronal population in the basal ganglia, responsible for the interaction between two types of neurotransmitters, GABA and acetylcholine.
The study has just been published in Cell reports.
The striatum is the main input structure to the basal ganglia, a region of the brain involved in a variety of sensorimotor functions and reinforcement learning. 99% of striatal neurons are inhibitory GABAergic cells, and the only exception is the population of cholinergic interneurons.
“In previous studies, we have shown the interactions between cholinergic interneurons and the dopaminergic system, and here we focused on the interactions between the cholinergic and GABAergic systems in the striatum,” says Gilad Silberberg, professor in the Department of Neuroscience and lead author of the study.
The striatum is strongly modulated by acetylcholine and early treatment of Parkinson’s disease relied on the cholinergic system. Cholinergic interneurons have been shown to alter their activity in Parkinson’s disease, Huntington’s disease, and in various forms of dyskinesia, all of which are disorders related to striatal function.
“Here, we wanted to investigate how cholinergic activity shapes striatal activity via nicotine receptors, a specific acetylcholine receptor,” says Anna Tokarska, Ph.D. student in the Silberberg lab and first author of the study.
“To do this, we used transgenic mice, marking the striatal interneurons expressing these nicotinic receptors via the Chrna2 gene. We could then use various methods, including patch clamp and optogenetics, to characterize these neurons and their synaptic connectivity in the striatum,” she continues.
The population of striatal Chrna2 interneurons was highly diverse, comprising at least three major subpopulations with distinct anatomical and electrical properties. One population was of particular interest, showing novel characteristics, including a strong response to acetylcholine.
The next steps in this line of research will be to study this population in more detail, including its involvement in striatal function and dysfunction.
About this neuroscience research news
Original research: Free access.
“GABAergic interneurons expressing the α2 nicotinic receptor subunit are functionally integrated into the striatal microcircuit” by Anna Tokarska et al. Cell reports
GABAergic interneurons expressing the α2 nicotinic receptor subunit are functionally integrated into the striatal microcircuit
- Triple whole-cell recordings are used to study striatal interneurons in Chrna2-Cre mice
- Unlike other brain regions, most striatal Chrna2 interneurons express parvalbumin
- Three distinct subtypes of striatal Chrna2 interneurons are defined
- Their synaptic connectivity is mapped using optogenetics and patch-clamp recordings
Interactions between the striatal cholinergic and GABAergic systems are crucial in shaping reward-related behavior and reinforcement learning; however, the synaptic pathways that mediate them are largely unknown.
Here, we use Chrna2-Cre mice to characterize striatal interneurons (IN) expressing the α2 nicotinic receptor subunit.
Using triple patch-clamp recordings combined with optogenetic stimulations, we characterize the electrophysiological, morphological and synaptic properties of striatal Chrna2-INs.
Striatal Chrna2-INs have diverse electrophysiological properties, distinct from their counterparts in other brain regions, including the hippocampus and neocortex.
Unlike other regions, most striatal Chrna2-INs are fast-spiking INs expressing parvalbumin. Striatal Chrna2-INs are intricately embedded in the striatal microcircuit, forming inhibitory synaptic connections with striatal projection neurons and INs, including other Chrna2-INs. They receive excitatory inputs from the primary motor cortex mediated by AMPA and NMDA receptors.
A subpopulation of Chrna2-IN responds to nicotine intake, suggesting reciprocal interactions between this population of GABAergic interneurons and striatal cholinergic synapses.
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