Summary: Researchers characterize a novel neural 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 Neuroscience at Karolinska Institutet characterizes a novel neuronal population in the basal ganglia that is responsible for the interaction between two types of neurotransmitters, GABA and acetylcholine.
The study was recently published in cell reports.
The striatum is the main input structure to the basal ganglia, a brain region 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 dopamine system, and here we have focused on the interactions between the cholinergic and GABAergic systems in the striatum,” explains Gilad Silberberg, a 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 various forms of dyskinesia, all of which are disorders associated with striatal function.
“Here we wanted to study how cholinergic activity affects striatal activity via nicotinic receptors, a specific acetylcholine receptor,” says Anna Tokarska, Ph.D. Student in the Silberberg laboratory and first author of the study.
“To do this, we used transgenic mice and labeled the striatal interneurons that express these nicotinic receptors through the Chrna2 gene. We could then use different 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 new characteristics including a strong response to acetylcholine.
Future steps in this research area will be to study this population more closely, including its involvement in striatal function and dysfunction.
About this news from neuroscientific research
Author: press office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Picture: The picture is attributed to Anna Tokarska, Gilad Silberberg
Original research: Open access.
“GABAergic interneurons expressing the α2-nicotinic receptor subunit are functionally integrated into the striatal microcirculation” by Anna Tokarska et al. cell reports
GABAergic interneurons expressing the α2-nicotinic receptor subunit are functionally integrated into the striatal microcirculation
- Triple whole cell recordings are used to examine 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
The interactions between the striatal cholinergic and GABAergic systems are critical 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 (INs) 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 distinct electrophysiological properties that differ from their counterparts in other brain regions, including the hippocampus and neocortex.
Unlike in other regions, most striatal Chrna2 INs are rapidly increasing INs expressing parvalbumin. Striatal Chrna2-INs are intricately integrated into the striatal microcirculation and form inhibitory synaptic connections with striatal projection neurons and INs, including other Chrna2-INs. They receive excitatory inputs from the primary motor cortex mediated by both AMPA and NMDA receptors.
A subpopulation of Chrna2-INs responds to nicotine intake, suggesting mutual interactions between this GABAergic interneuron population and striatal cholinergic synapses.