Biology subjects

McKie, I.

Publications and source records attributed to McKie, I..

4 recordsLinked to original sources

bioRxiv2026

Adversity severity shapes caregiving predictors and neural correlates of infant social behavior

Early-life adversity is associated with highly variable developmental outcomes, but identifying sources of this heterogeneity is difficult because variation in outcome is typically accompanied by variation in exposure. Animal models provide experimental leverage by standardizing features of the early environment while allowing variation in developmental experience and outcome to remain observable. Using a graded limited bedding and nesting model spanning normative rearing, moderate restriction, and severe scarcity, we asked what distinguishes social outcomes among animals exposed to the same resource restriction. Severe scarcity increased adverse maternal handling while leaving organized nurturing behaviors intact. Following the P8-P12 rearing manipulation, pups were tested outside the home cage in a P13 social approach assay. Severe scarcity reduced the proportion of pups that approached the dam, but outcomes varied substantially among scarcity litters. Greater typical maternal pup transport predicted greater approach, whereas a greater proportion of rough transport predicted poorer approach. Transport composition did not differ across rearing conditions, but its relationship with social behavior did. Amygdala intercalated-cell recruitment also covaried with social approach under severe scarcity despite limited condition-level differences in regional c-Fos. Plasma corticosterone differed across rearing conditions but did not covary detectably with the principal caregiving, behavioral, or neural measures. Maternal transport and intercalated-cell recruitment were not robustly associated, identifying separable experiential and neural correlates of behavioral variation. These findings show that standardizing an environmental constraint does not produce uniform developmental experience or outcome, and that caregiving experiences preserved across rearing conditions can distinguish social outcomes under severe scarcity.

neuroscience↗

bioRxiv2026

Bile acid signaling as a therapeutically tractable pathway linking early caregiving adversity to social behavior

Adverse early caregiving produces lasting changes in social behavior and increases vulnerability to psychiatric illness, yet the biological pathways through which these experiences become embedded during development remain poorly understood. Using two complementary rat models of early-life adversity (ELA), we combined behavioral phenotyping with serum metabolomics and basolateral amygdala (BLA) transcriptomics to identify bile acid biology as a candidate pathway associated with disrupted social development. In the Deconstructed Adversity Model (DAM), which dissociates adverse social experience from non-social stress, social adversity produced distinct behavioral alterations accompanied by sex-, age-, and adversity-dependent changes in peripheral bile acid and tryptophan metabolism together with sex-specific BLA gene co-expression networks associated with social behavior. These coordinated peripheral and central alterations converged on bile acid biology as a candidate pathway for pharmacological intervention. We next tested this prediction in the Scarcity Adversity Model via Limited Bedding (SAM-LB), where oral supplementation with chenodeoxycholic acid (CDCA), but not the related primary bile acid cholic acid (CA), during the adversity period rescued the infant affiliative social deficit produced by adverse caregiving. Together, these findings identify bile acid biology as a pharmacologically tractable pathway associated with the developmental consequences of adverse early caregiving and support further investigation of CDCA, an FDA-approved bile acid, as a candidate intervention for mitigating early social behavioral deficits.

neuroscience↗

bioRxiv2025

Direct interoceptive input to the insular cortex shapes learned feeding behavior

The insular cortex (insula) is an interoceptive hub, which senses internal states such as hunger, thirst, pain, and emotions. Previous studies suggest that the insula directly senses internal states, but the mechanisms remain elusive. We identified a population of leptin receptor-positive cells with a unique morphology in the insula (INSLepR). Based on leptins known role in signaling adiposity, we hypothesized that INSLepR neurons detect internal states to regulate food intake and body weight. Accordingly, we found that intra-insula leptin administration or optogenetic stimulation of INSLepR neurons impacts feeding behavior. Moreover, INSLepR neuron activity encodes feeding bouts in an internal-state dependent manner, and leptin alters insula neural dynamics in response to feeding, while also reshaping the transcriptome. Taken together, our data supports a model for direct interoceptive input to the insula, in which INSLepR cells integrate adiposity level signals to regulate feeding and body weight in a learned manner.

neuroscience↗

bioRxiv2024

INGEsT: An Open-Source Behavioral Setup for Studying Self-motivated Ingestive Behavior and Learned Operant Behavior

Ingestive behavior is driven by negative internal hunger and thirst states, as well as by positive expected rewards. Although the neural substrates underlying feeding and drinking behaviors have been widely investigated, they have primarily been studied in isolation, even though eating can also trigger thirst, and vice versa. Thus, it is still unclear how the brain encodes body states, recalls the memory of food and water reward outcomes, generates feeding/drinking motivation, and triggers ingestive behavior. Here, we developed an INstrument for Gauging Eating and Thirst (INGEsT), a custom-made behavioral chamber which allows for precise measurement of both feeding and drinking by combining a FED3 food dispenser, lickometers for dispensing liquid, a camera for behavioral tracking, LED light for optogenetics, and calcium imaging miniscope. In addition, in vivo calcium imaging, optogenetics, and video recordings are well synchronized with animal behaviors, e.g., nose pokes, pellet retrieval, and water licking, by using a Bpod microprocessor and timestamping behavioral and imaging data. The INGEsT behavioral chamber enables many types of experiments, including free feeding/drinking, operant behavior to obtain food or water, and food/water choice behavior. Here, we tracked activity of insular cortex and mPFC Htr3a neurons using miniscopes and demonstrate that these neurons encode many aspects of ingestive behavior during operant learning and food/water choice and that their activity can be tuned by internal state. Overall, we have built a platform, consisting of both hardware and software, to precisely monitor innate ingestive, and learned operant, behaviors and to investigate the neural correlates of self-motivated and learned feeding/drinking behaviors.

neuroscience↗