Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

Abstract

<jats:title>Abstract</jats:title><jats:p>Behavioural studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions based on their particular roles; however, anatomical evidence suggest that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioural-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a sharp boundary. Combining <jats:italic>in vivo</jats:italic> optopatch-clamp and extracellular recordings of spontaneous activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the slow and fast oscillations, due to particular cortico-striatal connectivity and local properties of each region. Additionally, distinct properties between striatonigral and striatopallidal neurons were revealed along DS. These results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.</jats:p>

Sensory responses in dorsolateral striatum are modulated by motor activity in a dopamine-dependent manner

“…We show that both MSN types respond to bilateral whisker stimulation in awake mice. These results are in agreement with whole-cell recordings in anesthetized mice 16,21,23 . A previous study using whole-cell recordings in awake mice reported that sensory responses in dMSNs were markedly larger than in iMSNs 20 , which was not the case in our data.…”

“…Another mechanism could be an increase in MSN membrane conductance due to synaptic input during whisking, and lastly, a decreased synaptic driving force due to membrane depolarization in MSNs. For instance, during up-states in anesthetized mice, a brain state characterized by depolarization and elevated synaptic input, sensory stimulation generates smaller responses in the MSNs than those evoked in the down-state 16,21 . Our data show that during whisking, MSNs undergo depolarization and increase in membrane conductance (Figures 3 and S3), both supporting the attenuation of synaptic responses.…”

“…The dorsolateral striatum (DLS) receives dense monosynaptic excitatory input from sensory cortical regions, including the barrel field, and is involved in sensory representation [13][14][15][16][17][18] . Striatal medium spiny neurons of both the direct-and indirect pathways (dMSNs and iMSNs, respectively) respond to whisker stimulation 16,[19][20][21][22][23] . Importantly, MSNs have distinct representations for contralateral and ipsilateral tactile inputs 16,23 , a feature that is lost following dopamine (DA) depletion, as shown in anesthetized mice 23 .…”

Striatal Direct Pathway Targets Npas1+Pallidal Neurons

“…The dStr is composed of molecularly, synaptically, and functionally distinct subdivisions (Flaherty and Graybiel, 1994;Smith et al, 2004;Palmiter, 2009, 2010;Pan et al, 2010;Nambu, 2011;Hintiryan et al, 2016;Hooks et al, 2018;Poulin et al, 2018;Martin et al, 2019;Alegre-Cortés et al, 2020;Ortiz et al, 2020). The dorsomedial striatum (DMS) and dorsolateral striatum (DLS) are thought to be involved in regulating goaldirected and habitual behavior, respectively (Yin and Knowlton, 2006;Balleine and O'Doherty, 2010;Redgrave et al, 2010;O'Hare et al, 2016;Malvaez and Wassum, 2018;Cox and Witten, 2019).…”

Striatal Direct Pathway Targets Npas1+Pallidal Neurons

“…The dStr is composed of molecularly, synaptically, and functionally distinct subdivisions (Flaherty and Graybiel, 1994; Smith et al, 2004; Darvas and Palmiter, 2009, 2010; Pan et al, 2010; Nambu, 2011; Hintiryan et al, 2016; Hooks et al, 2018; Poulin et al, 2018; Martin et al, 2019; Alegre-Cortés et al, 2020; Ortiz et al, 2020). The dorsomedial striatum (DMS) and dorsolateral striatum (DLS) are thought to be involved in regulating goal-directed and habitual behavior, respectively (Yin and Knowlton, 2006; Balleine and O’Doherty, 2010; Redgrave et al, 2010; Cox and Witten, 2019).…”