Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement

Abstract

Striatal pavalbumin (PV) and cholinergic (CHI) interneurons are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells has made it difficult to directly assess their contribution to activity in networks of MSNs during behavior. Here, we build upon recent improvements in single cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntarily locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.

A new GABAergic projection from the BNST onto accumbal parvalbumin neurons controls anxiety

“…Previous studies have showed that the NAc receives intermingled glutamatergic and dopaminergic inputs from a variety of forebrain regions, including the amygdala 23 , hippocampus 22 , thalamus 21, 33 , ventral tegmental area 19 and the prefrontal cortex 34 . Using Cre-dependent, rabies-virus-based whole brain monosynaptic tracing strategy and electrophysiological recordings from brain slices, we demonstrated that NAc PV cells were specifically innervated by the GABAergic afferents stemming from the adBNST (Fig.…”

“…To our best knowledge, this is the first study to map novel neural circuitry specifically innervating NAc PV neurons. Although a recent study found that light-evoked activation of vHPC inputs to NAc resulted in NAc PV cell regulation of cocaine-seeking behavior, a cell-specific monosynaptic tracing strategy was not used in their study to show the anatomic connection 22 . Therefore, we speculate that the PV response to vHPC afferent activation may be indirect.…”

“…One possibility is PV GABAergic interneurons, which comprise only 3-4% of all neurons in the NAc 19, 20 . In other brain regions, these neuron regulate fear response 21 , anxiolysis 22 , alcohol addiction 23 , and reward seeking 3, 24 . However, we know less about the function of accumbal PV neurons and the inputs they receive, and nothing about any possible role in anxiety related behavior.…”

Loss of the Er81 Transcription Factor in Cholinergic Cells Alters Striatal Activity and Habit Formation

“…CINs control habit formation via the synchronisation and strengthening of the activity of the striatal output neurons (Gritton et al, 2019) (O'Hare et al, 2016 (Yin et al, 2004) (Balleine, 2019). Strong pauses have been shown to emerge during learning in response to rewardassociated stimuli but not to neutral stimuli (Graybiel et al, 1994) (Morris et al, 2004).…”

“…Cholinergic interneurons (CINs) constitute only 1-2% of all striatal neurons but are the main source of acetylcholine in the striatum and play a crucial role in regulating motor learning and behavioural flexibility (Aoki et al, 2015) (Martos et al, 2017). Unique morphological and electrophysiological features (Lim et al, 2014) underpin CIN function in controlling the striatal output neurons (Mamaligas and Ford, 2016) (Gritton et al, 2019) ( Morris et al, 2004). CINs fire tonically and display phasic responses to stimuli, which consist of pauses preceded by a transient rise and followed by a ''rebound''of CIN activity (Apicella, 2017).…”