Adzemovic, A. | Search bioRxiv

bioRxiv2024

Prefrontal orchestration: a cortical network for rodent motor inhibition

Goal-directed action control and behavioral flexibility are prerequisites for effective, adaptive behavior. Both abilities rely on functional motor inhibition, which is linked to the prefrontal cortex (PFC), where distinct subsections collaborate in functional networks. How these PFC subsections interact and which roles they play during motor inhibition remains incompletely understood. In this study, we employed an action-preparation task in rats, combined with bidirectional optogenetic interventions, opto-fMRI, single unit electrophysiology and local field potential synchrony measurements across PFC subsections. Our findings support a clear and simple model of action inhibition within the prefrontal network. This model suggests prelimbic cortex (PL) as an input-dependent switch between motor inhibition and execution, modulated by an infralimbic cortex (IL)-dominated network. This distribution of tasks allows the PL to mediate goal-directed action while the IL ensures behavioral flexibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/618207v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@147ab98org.highwire.dtl.DTLVardef@52b6f9org.highwire.dtl.DTLVardef@6ab566org.highwire.dtl.DTLVardef@1ab5044_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Behavioral measurements were conducted alongside optogenetic modulation of PL, IL or VO. Inhibitory modulation led to varying effects on performance, while excitatory ChR2 stimulation of PL, IL or VO led to analogous effects on proactive motor inhibition. To identify shared nodes recruited by ChR2 stimulation of distinct PFC subareas, we performed whole-brain mapping with opto-fMRI. This revealed an overlapping activation volume spanning PFC, BF, Fr, Cg2, and M2. Notably, this common activation volume closely outlined the entirety of the IL-recruited regions; IL excitation also produced robust behavioral effects. Multisite recordings revealed task performance-dependent PL-IL delta synchrony. PCA of single-unit activity during behavior revealed varied neural patterns among PFC subsections, highlighting PL to have the most the homogenous input-driven activity. The findings can be interpreted as PL acting as an input-dependent switch between motor inhibition and execution, modulated by IL to maintain behavioral flexibility. C_FIG

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bioRxiv2023

Mechanisms of Premotor-Motor Cortex Interactions during Goal Directed Behavior

Deciphering the neural code underlying goal-directed behavior is a long-term mission in neuroscience1,2. Neurons exhibiting preparation and movement-related activity are intermingled in the premotor and motor cortices3,4, thus concealing the neural code of planned movements. We employed a combination of electrophysiology, pathway-specific optogenetics, phototagging, and inverse reinforcement learning (RL) to elucidate the role of defined neuronal subpopulations in the rat rostral and caudal forelimb areas (RFA and CFA), which correspond to the premotor and motor cortical areas. The inverse RL enabled the functional dissection of spatially intermingled neuronal subpopulations, complementing our pathway-specific optogenetic manipulations and unveiling differential functions of the preparation and movement subpopulations projecting from RFA to CFA. Our results show that the projecting preparation subpopulation suppresses movements, whereas the projecting movement subpopulation promotes actions. We found the influence of RFA on CFA to be adaptable, with the projection either inhibiting or exciting neurons in the superficial and deep CFA layers, depending on context and task phase. These complex interactions between RFA and CFA likely involve the differential recruitment of inhibitory interneurons in the CFA, which is supported by our electron microscopy analysis of the connectivity between these regions. We provide here unprecedented mechanistic insights into how the premotor and primary motor cortices are functionally and structurally interlinked with the potential to advance neuroprosthetics. Graphical abstractThis study provides mechanistic insights into the interactions between the rostral forelimb area (RFA) and the caudal forelimb area (CFA). Specifically, we provide evidence for a differential impact of RFA on CFA depending on the task phase and the targeted CFA layers. RFA contains at least two spatially intermingled subpopulations - one related to movement preparation and one to movement execution. Both subpopulations project to CFA. Here we investigated the impact of these two subpopulations on the activity of the local CFA circuit as well as on the behavior in different contexts. When rats were not involved in a task, the effect of RFA was mainly excitatory in the deep CFA layers, while the superficial layers remained unaffected. This can be interpreted as a non-selective activation of the deep CFA neurons enabling a variety of spontaneous movements. During the preparation phase before a movement, the RFA had an opposite impact on the superficial and deep layers: while the superficial CFA layers were excited by RFA input, the deeper layers were mostly inhibited, minimizing movements and enabling continued holding of a lever. During the movement phase, the inhibitory effect on neurons in the deep CFA layers was counterbalanced by excitation, thus enabling a selected conduction of movements. The opposing effects during preparation and movement phase on CFA deep layers were correlated with increased firing rates of the RFA preparation and movement subpopulations, respectively, making it likely that the inhibition resulted from increased activities of these subpopulation specifically. With an electron microcopy approach we demonstrate that inhibitory and excitatory CFA neurons are directly targeted by RFA, thus providing a mechanism for the bidirectional control of CFA activity. Please note that the depicted impact of RFA on excitatory or inhibitory CFA neurons refers to net effects in this figure, not to the targeting of individual neurons. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/524944v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@4de2d5org.highwire.dtl.DTLVardef@167164forg.highwire.dtl.DTLVardef@e9d298org.highwire.dtl.DTLVardef@101320b_HPS_FORMAT_FIGEXP M_FIG C_FIG

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