Biology subjects

Andrianarivelo, A.

Publications and source records attributed to Andrianarivelo, A..

3 recordsLinked to original sources

bioRxiv2025

A role for prefrontal dopamine signaling in control of goal-directed actions

Impairments in behavioral flexibility commonly found across psychiatric disorders have often been attributed to a dysfunction of the medial prefrontal cortex (mPFC), notably in relation with altered dopamine transmission. However, how dopamine transmission shapes neuronal activity in the mPFC to allow adapting to a changing situation remains largely elusive. Here, we show that dopamine dynamics in the mPFC encode the value of instrumental actions, in particular during reversal learning. Such signal shapes the activity of mPFC dopaminoceptive neurons during reversal learning through the recruitment of heteromers formed by dopamine D1 and D2 receptors with NMDA receptors. In accordance, blockade of either D1/NMDA or D2/NMDA heteromers in the mPFC selectively impairs reversal of outcome identities but not learning and expression of initial action-outcome associations. Our findings provide mechanistic evidence for a central role of dopamine in the mPFC to allow updating goal-directed actions.

neuroscience↗

bioRxiv2023

Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Locomotion in complex environments depends on the precise timing and active control of single paw movements in order to adapt steps to surface structure and coordinate paws. Such motor control crucially depends on the cerebellum, which is thought to support moment-to-moment prediction and correction of paw trajectories. Although cerebellar activity has been linked to limb kinematics on flat surfaces, it remains unknown how cerebellar cortical neurons encode paw movements when gait becomes irregular and the requirements for precise motor control vary dynamically. To address this question, we developed LocoReach: a new task which combines continuous and discrete aspects of motor control by requiring mice to walk on a runged treadmill, where each step involves reaching for the next rung. Over several days of learning, mice became increasingly proficient at LocoReach, so that they made fewer, longer strides with faster swings and fewer missteps. Through real-time optogenetic disruption of cerebellar processing, we shortened the swing of the perturbed paw highlighting the online contribution of lobule simplex to precise limb control the task. We next investigated the role of the cerebellar lobule simplex during LocoReach learning using electrophysiological recordings, with particular focus on molecular layer interneurons (MLIs) that shape the timing and gain of Purkinje cell (PC) output. When analyzing behaviorally-evoked responses in MLIs and PCs, we found sharp changes in activity around paw-specific transitions from swing to stance and vice versa. Cells in lobule simplex showed clear behavioral specificity: most neurons were tuned to swing-stance transitions of the ipsilateral paw, a large proportion encoded transitions of other or even multiple paws. Specifically MLIs exhibited larger amplitude firing-rate changes during longer strides acquired through learning, indicating increased engagement during higher-demand steps. These results show that cerebellar activity is tightly aligned to defined events in the step cycle, providing a mechanism through which cerebellar cortical circuits can contribute to the precise control of paw placement during adaptive locomotion.

neuroscience↗

bioRxiv2021

Cell type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons

The persistent and experience-dependent nature of drug addiction may result in part from epigenetic alterations, including non-coding micro-RNAs (miRNAs), which are both critical for neuronal function and modulated by cocaine in the striatum. Two major striatal cell populations, the striato-nigral and striato-pallidal projection neurons, express respectively the D1 (D1-SPNs) and D2 (D2-SPNs) dopamine receptor, and display distinct but complementary functions in drug-evoked responses. However, a cell-type-specific role for miRNAs action has yet to be clarified. Here, we evaluated the expression of a subset of miRNAs proposed to modulate cocaine effects in the nucleus accumbens (NAc) and dorsal striatum (DS) upon sustained cocaine exposure in mice and showed that these selected miRNAs were preferentially up-regulated in the NAc. We then focused on miR-1 considering the important role of some of its predicted mRNA targets, such as fosb and npas4, in the effects of cocaine. We validated these targets in vitro and in vivo and further showed that overexpression of miR-1 in D1-SPNs of the DS reduced cocaine-induced CPP reinstatement, whereas it increased cue-induced reinstatement of cocaine-SA, without affecting other cocaine-mediated adaptive behavior. In addition, miR-1 overexpression in D2-SPNs of the DS reduced the motivation to self-administer cocaine but did not modify other measured behaviors. Together, our results highlight a precise cell-type- and region-specific control of relapse to cocaine-seeking behaviors by miR-1, and illustrate the importance of cell-specific investigations.

neuroscience↗