Disinhibition of the Nucleus Accumbens Leads to Macro-Scale Hyperactivity Consisting of Micro-Scale Behavioral Segments Encoded by Striatal Activity

Abstract

The striatum comprises of multiple functional territories involved with multilevel control of behavior. Disinhibition of different functional territories leads to territory-specific hyperkinetic and hyperbehavioral symptoms. The ventromedial striatum, including the nucleus accumbens (NAc) core, is typically associated with limbic input but was historically linked to high-level motor control. In this study, performed in female Long-Evans rats, we show that the NAc core directly controls motor behavior on multiple timescales. On the macro-scale, following NAc disinhibition, the animals manifested prolonged hyperactivity, expressed as excessive normal behavior, whereas on the micro-scale multiple behavior transitions occurred, generating short movement segments. The underlying striatal network displayed population-based local field potential transient deflections (LFP spikes) whose rate determined the magnitude of the hyperactivity and whose timing corresponded to unitary behavioral transition events. Individual striatal neurons preserved normal baseline activity and network interactions following the disinhibition, maintaining the normal encoding of behavioral primitives and forming a sparse link between the LFP spikes and single neuron activity. Disinhibition of this classically limbic territory leads to profound motor changes resembling hyperactivity and attention deficit. These behavioral and neuronal results highlight the direct interplay on multiple timescales between different striatal territories during normal and pathological conditions. The nucleus accumbens (NAc) is a key part of the striatal limbic territory. In the current study we show that this classically limbic area directly controls motor behavior on multiple timescales. Focal disinhibition of the NAc core in freely behaving rats led to macro-scale hyperactivity and micro-scale behavioral transitions, symptoms typically associated with attention deficit hyperactivity disorder. The behavioral changes were encoded by the striatal LFP signal and single-unit spiking activity in line with the neuronal changes observed during tic expression following disinhibition of the striatal motor territory. These results point to the need to extend the existing parallel functional pathway concept of basal ganglia function to include the study of limbic-motor cross-territory interactions in both health and disease.

Dissociation of tic generation from tic expression during the sleep-wake cycle

“…The dissociation between LFP spikes and tic expression was first documented by Muramatsu et al, where striatal LFP spikes remained present after the cooling or lesioning of the cortex, whereas motor tics were not detectible in the EMG signal (Muramatsu et al, 1990;McCairn et al, 2016). A similar dissociation was also documented in our lab model of hyperactivity, in which striatal disinhibition was limited to the limbic region (Yael et al, 2019). In this case, the abnormal behavior involved overall increased locomotion, whereas the LFP spikes were partially correlated with movement stops.…”

An arbiter model of motivational selection

“…Excitation of PVT can also disrupt behaviour under this conflict but because it suppresses selection of behaviour. This effect of PVT excitation would be the opposite, but complementary, to the non-selective increases in frequency of normal behavior (Yael et al, 2019) and neural activity (Millan et al, 2010) observed after non-selectively inhibiting Acb and is worth further investigation (e.g., Chisholm et al, 2019).…”

Enhanced habit formation in Tourette syndrome: dopamine release and striatal disinhibition modulate shortcut connections in a hierarchical model of cortico-basal ganglia loops

“…In the current implementation of the model, the dorsomedial loop receives a desired goal signal (here, a desired outcome fruit) and an associated stimulus signal (observed box with fruit icon) as inputs (Figure 2A). Although the goal selection process is not explicitly modeled, we assume that it involves the limbic network (Groenewegen et al, 1997(Groenewegen et al, , 1999Corbit et al, 2001;Balleine et al, 2003;Gönner et al, 2017), including the ventral striatum (Yael et al, 2019). The dorsomedial loop uses reward signals to learn to select an intended button which is transferred to the dorsolateral loop as a reference signal.…”