A Low-Correlation Resting State of the Striatum during Cortical Avalanches and Its Role in Movement Suppression

Abstract

During quiet resting behavior, involuntary movements are suppressed. Such movement control is attributed to cortico-basal ganglia loops, yet population dynamics within these loops during resting and their relation to involuntary movements are not well characterized. Here, we show by recording cortical and striatal ongoing population activity in awake rats during quiet resting that intrastriatal inhibition maintains a low-correlation striatal resting state in the presence of cortical neuronal avalanches. Involuntary movements arise from disturbed striatal resting activity through two different population dynamics. Nonselectively reducing intrastriatal γ-aminobutyric acid (GABA) receptor-A inhibition synchronizes striatal dynamics, leading to involuntary movements at low rate. In contrast, reducing striatal interneuron (IN)-mediated inhibition maintains decorrelation and induces intermittent involuntary movements at high rate. This latter scenario was highly effective in modulating cortical dynamics at a subsecond timescale. To distinguish intrastriatal processing from loop dynamics, cortex-striatum-midbrain cultures, which lack feedback to cortex, were used. Cortical avalanches in vitro were accompanied by low-correlated resting activity in the striatum and nonselective reduction in striatal inhibition synchronized striatal neurons similar to in vivo. Importantly, reduction of inhibition from striatal INs maintained low correlations in the striatum while reorganizing functional connectivities among striatal neurons. Our results demonstrate the importance of two major striatal microcircuits in distinctly regulating striatal and cortical resting state dynamics. These findings suggest that specific functional connectivities of the striatum that are maintained by local inhibition are important in movement control.

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

“…Similar manipulations in the limbic part of the striatum lead to hyperactivity expressed as increased normal behavior, which is nonspecific to a body part and is expressed bilaterally. Disinhibition of the sensorimotor territory in the striatum was shown to lead to the appearance of LFP spikes and phase-locked individual neuronal activity which were correlated with the appearance of individual tics (Bronfeld et al, 2013;Israelashvili and Bar-Gad, 2015;Pogorelov et al, 2015;Klaus and Plenz, 2016). The timing of individual LFP spikes was correlated with unitary behavioral events, individual tics, resembling the correlation to individual movement terminations in the current study.…”

“…In addition, disinhibition of the NAc shell led to emotional dysregulation (Stratford and Kelley, 1997;Lopes et al, 2012), which may contribute indirectly to the observed changes in locomotion. Multiple different hyperkinetic states have been evoked using similar manipulations in the sen-sorimotor basal ganglia: disinhibition of the sensorimotor striatum leads to motor tics (Tarsy et al, 1978;McCairn et al, 2009;Bronfeld et al, 2013;Pogorelov et al, 2015;Klaus and Plenz, 2016), downstream disinhibition in the sensorimotor GPe leads to chorea (Grabli et al, 2004;Bronfeld et al, 2010) and disinhibition of the striatum in cats (Yamada et al, 1995), and the motor thalamus in primates (Guehl et al, 2000) leads to dystonia. The disinhibition of sensorimotor territories share common properties: they lead to the expression of different hyperkinetic symptoms in the form of abnormal movements, which are not part of the normal animal's repertoire, are specific to body part, and are expressed unilaterally contralateral to the injected hemisphere.…”

Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors

“…The diffusion coefficient of all other molecules was set to D* ϭ 5e-8 cm 2 /s (Li et al, 2015). The initial conditions (Table 6) and reactions (Table 7) were modeled according to the kinetic schemes reported by Fernandez et al (2006) to which we added new reactions for pDARPP-32 S97 . Briefly, DARPP-32 is phosphorylated in position T34 by the cAMP-dependent protein kinase A (PKA; pDARPP-32 T34 ), in position T75 by the cyclindependent kinase 5 (CdK5; pDARPP-32 T75 ), in position S97 by casein kinase 2 (CK2; pDARPP-32 S97 ), and in position S130 by casein kinase 1 (CK1; pDARPP-32 S130 ).…”

“…We tested directly the hypothesis that EAAC1 controls striatal function ex vivo by obtaining extracellular field recordings in acute brain slices containing the DLS, a domain of the striatum specifically implicated with habit learning (Barnes et al, 2005;Yin et al, 2005;Yin et al, 2006). We stimulated excitatory synaptic afferents by positioning a bipolar stimulating electrode in the DLS 100 -200 m away from the recording electrode ( Fig.…”

“…Persistent thoughts, anxiety, and repeated execution of stereotyped movements are hallmark features of neuropsychiatric disorders such as obsessive-compulsive disorder (OCD) (Kessler et al, 2005). Family-based linkage analyses identify the gene Slc1a1, which encodes the neuronal glutamate transporter EAAC1, as one of the strongest candidate genes for OCD (Hanna et al, 2002;Arnold et al, 2006;Dickel et al, 2006;Stewart et al, 2007;Shugart et al, 2009;Wendland et al, 2009;Samuels et al, 2011). Alternative isoforms of Slc1a1 that are differentially regulated in OCD patients have been shown to impair glutamate uptake via EAAC1 (Porton et al, 2013).…”