Biology subjects

Concetti, C.

Publications and source records attributed to Concetti, C..

4 recordsLinked to original sources

bioRxiv2026

Melanin-concentrating hormone signaling regulates persistence and updating of reward-guided actions

Flexible behavior requires persistence when a strategy remains effective and rapid updating when its consequences change. Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus regulate feeding, reward and memory, but their contribution to reward guided flexibility is unknown. Here, mice learned an action-outcome contingency in a T-maze and then adapted when the reward location switched. MCHR1 antagonism throughout learning did not measurably alter Initial Learning but reduced perseverative choices and accelerated behavioral adaptation after the contingency switched. Endogenous LH-MCH activity was strongest while contingencies were being established or revised, declined as performance stabilized, distinguished rewarded from unrewarded outcomes, and reflected current outcomes in the context of recent and accumulated experience. MCHR1 blockade altered prelimbic responses to successful outcomes in both phases and opposed their progressive weakening during Rule Switch. Together, these findings identify MCH signaling as a regulator of how strongly past reward continues to guide behavior when contingencies change and reveal accompanying changes in prefrontal processing of successful outcomes.

neuroscience↗

bioRxiv2023

Exploratory rearing is governed by hypothalamic MCH cells according to the locus coeruleus

Exploration is essential for survival because it allows animals to gather information about their environment. Rearing is a classic exploratory behavior, during which an animal transiently stands on its hind legs to sample its environment. It is widely observed in common lab conditions as well as in the wild, yet neural signals and circuits underlying this fundamental component of innate behavior remain unclear. We examined behavioral correlates of activity in hypothalamic MCH-producing neurons (MNs) - a recently characterized but still poorly understood neural type - and found that MN activation co-occurs with exploratory rears in mice. Complementary optogenetic and pharmacological manipulations indicated that MN activity selectively promotes rearing via G-protein coupled MCHR1 receptors. Furthermore, we show in vivo that activation of the locus coeruleus noradrenergic neurons rapidly inhibits MNs and suppresses rearing through MCHR1-dependent pathways. Overall, these findings define a subcortical neural module which both tracks and controls exploratory rearing.

neuroscience↗

bioRxiv2022

A role for MCH neuron firing in hippocampal plasticity and learning

It has been revealed that melanin-concentrating hormone (MCH) neurons in the hypothalamus can influence learning (Liu et al., 2022) and memory formation (Kosse & Burdakov, 2019), but the cellular mechanisms by which they perform this function are not understood. Here, we examine the role of MCH neural input to the hippocampus, and show in vitro that optogenetically increasing MCH axon activity facilitates hippocampal plasticity by lowering the threshold for synaptic potentiation. In vivo, we find that MCH neurons are naturally active in response to reinforcing cues during a spatial learning task, and that this activity is correlated with the speed of learning. Together, our results align with increasing evidence that MCH neurons play an on-line regulatory role in learning, and reveal that this could be achieved through modulation of synaptic plasticity in the hippocampus.

neuroscience↗

bioRxiv2018

Apical progenitors remain multipotent throughout corticalneurogenesis

The diverse subtypes of excitatory neurons that populate the neocortex are born from progenitors located in the ventricular zone (apical progenitors, APs). During corticogenesis, APs progress through successive temporal states to sequentially generate deep- followed by superficial-layer neurons directly or via the generation of intermediate progenitors (IPs). Yet little is known about the plasticity of AP temporal identity and whether individual progenitor subtypes remain multipotent throughout corticogenesis. To address this question, we used FlashTag (FT), a method to pulse-label and isolate APs in the mouse neocortex with high temporal resolution to fate-map neuronal progeny following heterochronic transplantation of APs into younger embryos. We find that unlike daughter IPs, which lose the ability to generate deep layer neurons when transplanted into a younger host, APs are temporally uncommitted and become molecularly respecified to generate normally earlier-born neuron types. These results indicate that APs are multipotent cells that are able to revert their temporal identity and re-enter past molecular and neurogenic states. AP fate progression thus occurs without detectable fate restriction during the neurogenic period of corticogenesis. These findings identify unforeseen cell-type specific differences in cortical progenitor fate plasticity, which could be exploited for neuroregenerative purposes.

neuroscience↗