Biology subjects

Potter, L. E.

Publications and source records attributed to Potter, L. E..

3 recordsLinked to original sources

bioRxiv2025

Bidirectional modulation of accumbens dopamine by MCH neurons during learning and consummatory behavior

The formation of sensory cue-reward associations is essential for survival, but in the modern calorie-rich and advertising-intensive environment, such associations may become maladaptive - leading to negative health consequences such as obesity or diabetes. Recent research has demonstrated the importance of hypothalamic melanin-concentrating hormone (MCH)-expressing neurons in driving hedonically-motivated feeding and in forming these associations. The MCH system interacts with mesolimbic dopamine (DA) transmission, offering a potential mechanism for the effects of MCH neurons on hedonic feeding and associative conditioning. However, this interaction has not been fully characterized in vivo with modern approaches that offer high temporal and spatial resolution. We characterized MCH-DA interactions during feeding and food- motivated Pavlovian conditioning using in vivo fiber photometry in the lateral hypothalamus/zona incerta (LH/ZI) and nucleus accumbens (NAc). We found that MCH neuron activity and DA release in the medial-shell of the NAc (mNAcSh) were co-activated during consumption and in response to reward-predicting cues. During consumption, DA release preceded MCH activity, while responses to reward-predicting cues emerged in MCH neurons earlier than in the DA system. Lastly, gain and loss-of function of the MCH system bidirectionally modulates DA release in the mNAcSh. These results indicate that physiological co-activation of the MCH and DA systems occurs during food-motivated learning, and demonstrate a capacity for bidirectional modulation of DA release in the mNAcSh by the MCH system.

neuroscience↗

bioRxiv2022

Estradiol mediates stress-susceptibility in the male brain

In susceptible populations, stress is a major risk factor for the development of mental disorders, including depression. Estradiol, often considered a female hormone, is distributed in the male brain via aromatization of testosterone. The role of estrogen receptors (ERs) in male stress susceptibility and depression is not well understood. We found that absence of ER{beta} is associated with susceptibility to stress in male mice and that activity of ER{beta}-projecting neurons from the basolateral amygdala to nucleus accumbens is reduced in hypogonadal mice subjected to stress, while activation of this circuit reverses stress-induced maladaptive behaviors. We identified that absence of estradiol, but not testosterone per se, underlies stress susceptibility and that brain-selective delivery of estradiol prevents the development of depression-related behaviors. Our findings provide evidence for an estrogen-based mechanism underlying stress susceptibility and offer an unexpected therapeutic strategy for treating depression in males.

neuroscience↗

bioRxiv2022

Experimenter sex modulates mouse biobehavioural and pharmacological responses

Differential rodent responses to the sex of human experimenters could have far reaching consequences in preclinical studies. Here, we show that the sex of human experimenters affects mouse behaviours and responses to the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. We found that mice manifest aversion to human male odours, preference to female odours, and increased susceptibility to stress when handled by male experimenters. This male induced aversion and stress susceptibility is mediated by the activation of brain corticotropin-releasing factor (CRF) neurons projecting from the entorhinal cortrex to hippocampal area CA1. We further establish that exposure to male scent prior to ketamine administration activates CRF neurons projecting from the entorhinal cortex to hippocampus, and that CRF is necessary and sufficient for ketamines in vivo and in vitro actions. Further understanding of the specific and quantitative contributions of the sex of human experimenters to different experimental outcomes in rodents may lead not only to reduced heterogeneity between studies, but also increased capability to uncover novel biological mechanisms.

neuroscience↗