Biology subjects

Le Bon-Jego, M.

Publications and source records attributed to Le Bon-Jego, M..

3 recordsLinked to original sources

bioRxiv2023

Age-dependent modulation of the excitability of layer V pyramidal neurons by dopamine D1 receptors in mices primary motor cortex

The primary motor cortex (M1) receives dopaminergic (DAergic) projections from the midbrain which play a key role in modulating motor and cognitive processes, such as motor skill learning. However, little is known at the level of individual neurons about how dopamine (DA) and its receptors modulate the intrinsic properties of the different neuronal subpopulations in M1 and if this modulation depends on age. Using immunohistochemistry, we first mapped the cells expressing the DA D1 receptor across the different layers in M1, and quantified the number of pyramidal neurons (PNs) expressing the D1 receptor in the different layers, in young and adult mice. This work reveals that the spatial distribution and the molecular profile of D1 receptor-expressing neurons across M1 layers do not change with age. Then, combining whole-cell patch-clamp recordings and pharmacology, we explored ex vivo in young and adult mice the impact of activation or blockade of D1 receptors on PN intrinsic properties and identified a distinct modulation of intrinsic electrical properties of layer V PNs by D1 receptors depending on the age of the animal. HighlightsO_LIThe laminar distribution in M1 of cells expressing the dopamine D1 receptor is similar in young and adult mice C_LIO_LIMost of D1R-expressing cells in M1 also express Satb2 C_LIO_LID1R activation increases M1 layer V pyramidal neurons excitability both in young and adult mice C_LIO_LIThe effect of D1R blockade on M1 layer V pyramidal neurons excitability differs between young and adult mice C_LI

neuroscience↗

bioRxiv2022

Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut.

Whereas axons deprived of their nucleus degenerate within a few days in Mammals, they survive for several months in Crustacean. However, it is not known if central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity, after peripheral axotomy, which suppress their nucleus. Using electrophysiology techniques and electron microscopy imaging we report that 1) Electron microscopy analysis confirms previous observations that glial cell nucleus present in sensory nerve, proliferate an migrate to axon tubes, in which they form close contact with surviving axons; 2) after peripheral axotomy performed in vivo on Coxo-Basipodite chordotonal organ (CBCO) sensory nerve does not convey any sensory message, but antidromic volleys are observed; 3) Central synaptic transmission to motoneurons (MNs) progressively declines over #200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of polysynaptic inhibitory transmission persist up to 6 months). After #200 days no transmission is observed anymore; 4) However, this total loss is only apparent, because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials (IPSPs) then excitatory post-synaptic potentials (EPSPs); 5) The loss of synaptic transmission can be prevented by in vivo chronic sensory nerve stimulation; 6) Using simulations based on the geometric arrangements of synapses of the monosynaptic excitatory transmission and disynaptic inhibitory pathways, we have shown that antidromic activity in CBCO nerve could play a role in maintenance of synaptic function of inhibitory pathways to MNs, but not on monosynaptic excitatory transmission to MNs. Taken together, our study confirms the key role of glial nucleus in axon survival, that machinery for spike conduction and synaptic release even if no activity is present for several months. After long silence periods (>6 months) spike conduction and synaptic function can still be restored by electrical activity.

neuroscience↗

bioRxiv2019

Dopamine D2 receptors modulate intrinsic properties and synaptic transmission of parvalbumin interneurons in the mouse primary motor cortex

Dopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.\n\nSignificance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.

neuroscience↗