Biology subjects

Kosse, C.

Publications and source records attributed to Kosse, C..

3 recordsLinked to original sources

bioRxiv2024

Leptin Activated Hypothalamic BNC2 Neurons Acutely Suppress Food Intake

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism1. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons2. However, while AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect3-5. This has raised the possibility that there is a heretofore unidentified leptin-regulated neural population that suppresses appetite on a rapid time scale. Here, we report the discovery of a novel population of leptin-target neurons expressing basonuclin 2 (Bnc2) that acutely suppress appetite by directly inhibiting AGRP neurons. Opposite to the effect of AGRP activation, BNC2 neuronal activation elicited a place preference indicative of positive valence in hungry but not fed mice. The activity of BNC2 neurons is finely tuned by leptin, sensory food cues, and nutritional status. Finally, deleting leptin receptors in BNC2 neurons caused marked hyperphagia and obesity, similar to that observed in a leptin receptor knockout in AGRP neurons. These data indicate that BNC2-expressing neurons are a key component of the neural circuit that maintains energy balance, thus filling an important gap in our understanding of the regulation of food intake and leptin action.

neuroscience↗

bioRxiv2023

A Simple Subcortical Feeding Circuit Linking Interoceptive Inputs to Consummatory Behavior

The brain processes an array of stimuli enabling the selection of an appropriate behavioural response but the neural pathways linking interoceptive inputs to outputs for feeding are poorly understood. Here we delineate a subcortical circuit in which brain-derived neurotrophic factor (BDNF) expressing neurons in the ventromedial hypothalamus (VMH) directly connect interoceptive inputs to motor centers controlling food consumption and jaw movements. VMHBDNF neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas of the jaw. When food is unavailable, VMHBDNF inhibition elicits consummatory behaviors directed at inanimate objects such as a wooden block and inhibition of mesencephalic trigeminal area (Me5) projections evokes rhythmic jaw movements. The activity of these neurons is decreased during food consumption and increases when food is in proximity but not consumed. Activity is also increased in obese animals and after leptin treatment. VMHBDNF neurons receive monosynaptic inputs from both agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neurons in the arcuate nucleus (Arc) and constitutive VMHBDNF activation blocks the orexigenic effect of AgRP activation. These data delineate an Arc[->]VMHBDNF[->]Me5 circuit that senses the energy state of an animal and regulates consummatory behaviors in a state dependent manner.

neuroscience↗

bioRxiv2019

Natural hypothalamic circuit dynamics underlying object memorization

Memorizing encountered objects is fundamental for normal life, but the underlying natural brain activity remains poorly understood. The hypothalamus is historically implicated in memory disorders, but whether and how its endogenous real-time activity affects object memorization remains unknown. We found that upon self-initiated object encounters, hypothalamic melanin-concentrating hormone (MCH) neurons emit dynamic, object-encounter-associated signals encoding object novelty. Optosilencing of these signals, performed in closed-loop with object encounters selectively during object memory acquisition, prevented the ability to recognize the previously encountered objects. Optogenetic and chemogenetic connectivity analyses demonstrated that local GAD65 neurons form an inhibitory GAD65[->]MCH microcircuit that controls the object-encounter-associated MCH cell signals. GAD65 cell optosilencing during object memory acquisition enhanced future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that natural, object-associated signals in genetically-distinct but interacting hypothalamic neurons differentially control whether the brain forms object memories.

neuroscience↗