Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior

Abstract

Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

Excitatory extrinsic afferents to striatal interneurons and interactions with striatal microcircuitry

“…Mallet et al . (, ) showed with in vivo juxtacellular recordings and labeling that striatal neurons that exhibit brief action potential waveforms are parvalbumin‐positive, consistent with previous in vitro data (Kawaguchi, ; Kawaguchi et al ., ; Koos & Tepper, ) and assumptions from in vivo recordings from many others (Berke et al ., ; Mallet et al ., , ; Schulz et al ., ; Lee et al ., ; O’ Hare et al ., ). Mallet et al .…”

Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency

“…GABAergic interneurons in the striatum play important roles in regulating network function and behaviors (Tepper et al, ). GABAergic PV‐positive fast spiking inhibitory interneurons constitute ~3% of the neuron population in rodent striatum, control the bursting of MSNs, and modulate the circuit output (O'Hare et al, ; Owen et al, ). In our model, the density and dendritic complexity of PV neurons are affected by Disc1 insufficiency.…”

“…In addition to the MSNs, there are GABAergic interneurons in the striatum that play important roles in regulating network function (Tepper et al, 2018). For example, parvalbumin (PV)-expressing fast-spiking interneurons control the bursting of MSNs and modulate the circuit output (O'Hare et al, 2017;Owen, Berke, & Kreitzer, 2018). We next examined the histochemical features of striatal PV-positive interneurons (Figure 8a).…”

Pitx3Null Mutant (Striatal Dopamine-Deficient) Mice Have Exaggerated Spiny Projection Neuron Responses to l-DOPA and D1 Agonism and Lack Baseline Striatonigral Spiking

“…(Heinricher in Microelectrode Recording in Movement Disorder Surgery, 2004 ed. ) Identification metrics in these cases have used primarily waveshape, and some combination of firing rates, ISI histograms, autocorrelograms,or peri-event rasters (Barnes et al, 2005, Mallet 2005, Kubota 2009, Schmitzer Torbert and Redish 2009, Tepper, 2010, Gittis et al, 2011, o'Hare et al, 2017, but these criteria are inconsistently seen, reflecting the lack of knowledge over clearly distinguishing FSI traits in vivo; unambiguous identification is rare (Tepper and Koos, 2017). Thus resolving the identity of these units potentially stands to shed new light on previous conclusions, e.g.…”

“…Parkinson's disease, drugs of abuse). (Gittis et al, 2011, Kubota et al, 2009, Lee et al, 2017, o'Hare et al, 2017 Aside from the inherent technical difficulties of electrophysiological recordings, focusing research questions on a particular subtype of neuron further decreases the likelihood of sampling from a population of interest. According to many publications (Graveland & Difiglia 1985, Saka 2002, Rymar et al 2004, interneurons represent <5% of total striatal neurons, which can further be broken down into different interneuron types; e.g.…”