Biology subjects

Kucukdereli, H.

Publications and source records attributed to Kucukdereli, H..

5 recordsLinked to original sources

bioRxiv2026

A Hypothalamic Pathway for Energy Conservation

Many animals utilize a survival strategy of hypothermia, inactivity, and a dramatic decrease in their energy metabolism when faced with a shortfall in energy supplies. Mice, for example, show daily torpor that may last several hours to bridge the lack of energy availability in a cold environment. While our recent studies identified a population of neurons in the median preoptic nucleus (MnPO) necessary for fasting-induced torpor regulation, the specific brain circuits that trigger energy conservation in response to food restriction are unknown. We show here that the energy state of the animal is conveyed to preoptic neurons by inputs from the arcuate nucleus (ARC), a region known to be indispensable for driving metabolic and behavioral adaptations to the fasted state. We first found that the activity of ARC neurons expressing Agouti-Related Peptide (ARCAgRP) is required for the generation of fasting-induced torpor. Then, we showed that torpor-active ARCAgRP neurons innervate the preoptic area of the hypothalamus (POA), including the MnPO. Using optogenetic methods, we also found that activating the ARCAgRP-MnPO pathway induces key features of torpor: decreased body temperature, bradycardia, reduction of energy expenditure, and suppression of brown adipose tissue thermogenesis. Remarkably, we also show that inhibition of the ARCAgRP-MnPO brain circuit entirely prevents fasting-induced torpor. Furthermore, we identified that both NPY and GABA are neuromodulators used by ARCAgRP neurons to enable hypothermic responses during starvation. Our studies provide a detailed view of a hypothalamic pathway enabling energy conservation, a survival mechanism in conditions of low energy availability.

neuroscience↗

bioRxiv2025

Brainstem sensing of multiple body signals during food consumption

Studies of body-to-brain communication often examine one stimulus or organ at a time, yet the brain must integrate many body signals during behavior. For example, food consumption generates diverse oral and post-oral chemical and mechanical signals transduced by well-characterized peripheral neuronal pathways. Far less is known about how these and other bodily signals are integrated and organized in the brainstem lateral parabrachial nucleus (LPBN), a key interoceptive sensory hub. We established methods to image the activity of 1000s of neurons throughout a large region of mouse LPBN. Food consumption drove a seconds-long wave of activity across LPBN, with dynamics mirroring the movement of food through the upper gastrointestinal tract observed using X-ray fluoroscopy. By imaging the same neurons across days, we found that spatially clustered subsets of neurons encoded oral signals, stomach filling, visceral malaise, arousal, and/or body movement. Moreover, only certain subsets were modulated by cortical input. Together, these experiments reveal a functional specialization in the LPBN that integrates contextual information from the body to guide behavior.

neuroscience↗

bioRxiv2023

Chronic stress triggers seeking of a starvation-like state in anxiety-prone female mice

Elevated anxiety often precedes anorexia nervosa and persists after weight restoration. Patients with anorexia nervosa often describe hunger as pleasant, potentially because food restriction can be anxiolytic. Here, we tested whether chronic stress can cause animals to prefer a starvation-like state. We developed a virtual reality place preference paradigm in which head-fixed mice can voluntarily seek a starvation-like state induced by optogenetic stimulation of hypothalamic agouti-related peptide (AgRP) neurons. Prior to stress induction, male but not female mice showed mild aversion to AgRP stimulation. Strikingly, following chronic stress, a subset of females developed a strong preference for AgRP stimulation that was predicted by high baseline anxiety. Such stress-induced changes in preference were reflected in changes in facial expressions during AgRP stimulation. Our study suggests that stress may cause females predisposed to anxiety to seek a starvation state, and provides a powerful experimental framework for investigating the underlying neural mechanisms.

neuroscience↗

bioRxiv2019

State-specific gating of salient cues by midbrain dopaminergic input to basal amygdala

Basal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli that predict salient appetitive or aversive outcomes. We examined the learning- and state-dependent dynamics of BA neurons and ventral tegmental area dopamine axons that innervate BA (VTADA[->]BA) using two-photon imaging and photometry in behaving mice. BA neurons did not respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards or punishments. Most VTADA[->]BA axons were activated by both rewards and punishments, and acquired responses to cues predicting these outcomes during learning. Responses to cues predicting food rewards in VTADA[->]BA axons and BA neurons in hungry mice were strongly attenuated following satiation, while responses to cues predicting unavoidable punishments persisted or increased. Therefore, VTADA[->]BA axons may provide a reinforcement signal of motivational salience that invigorates adaptive behaviors by promoting learned responses to appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons.

neuroscience↗

bioRxiv2017

Central Amygdala Circuits Modulate Food Consumption Through A Positive Valence Mechanism

The complex behaviors underlying the pursuit and consumption of rewards are integral to an organisms survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is not well understood. The central nucleus of the amygdala (CeA) is implicated in feeding and reward behavior, but the specific neural players and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we define the neuronal mechanisms by which the CeA promotes consumption of food. We show, using in vivo activity manipulations and Ca2+ imaging, that CeA GABAergic neurons expressing the serotonin receptor 2a (Htr2a) modulate food consumption in multiple contexts, promote positive reinforcement and are active in vivo during eating. We demonstrate using electrophysiology, anatomical tracing methods and in vivo optogenetics that both intra-CeA and long-range circuit mechanisms underlie these functional effects. Finally, we show that CeAHtr2a neurons are poised to regulate food consumption through inputs from feeding-relevant brain regions. Our study highlights a mechanism by which defined CeA neural circuits positively regulate food consumption.

neuroscience↗