Biology subjects

McDougall, S. J.

Publications and source records attributed to McDougall, S. J..

3 recordsLinked to original sources

bioRxiv2026

Stimulating a NTS to LC circuit elicits anxiety-like behavior andstate-dependent autonomic output.

Understanding how the brain integrates internal bodily signals to shape behavior is essential for characterizing the neural basis of interoception. Here, we investigate whether the nucleus of the solitary tract (NTS), a brainstem hub for viscerosensory input, communicates with the locus coeruleus (LC), a noradrenergic nucleus involved in arousal and cognition, to influence anxiety-like behavior. We utilized viral-induced optogenetics combined with electrocardiography and diaphragmatic electromyography to monitor heart rate and respiratory frequency. Prior to behavioral testing we photoactivated transduced NTS neurons either at their somata, or at their axonal terminals in the LC. Anxiety-related behaviors were assessed using the elevated plus maze (EPM) and novelty-suppressed feeding test (NSFT). Stimulation of the NTS somata, or their terminals in the LC, increased aspects of anxiety-like behaviors in the EPM and NSFT, including freezing time during the EPM and latency to eat in the center of the NSFT. Importantly, only NTS somal activation suppressed post-NSFT feeding. This suggests that the anxiety-like behaviors observed from activating NTS projections to the LC are not secondary to activating feeding circuits. Additionally, activation of NTS terminals in the LC altered heart rate and its variability following food deprivation. These findings reveal that the NTS to LC circuit enhances anxiety-like behavior and modulates cardiorespiratory dynamics state dependently, thereby identifying a likely brainstem pathway through which viscerosensory signals influence interoception.

animal behavior and cognition↗

bioRxiv2023

Re-coding of G protein-coupled receptor signaling enables emergent cellular behavior.

All cells face the challenge of integrating multiple extracellular signals to produce relevant physiological responses. Different combinations of G protein-coupled receptors, when co-expressed, can lead to distinct cellular outputs, yet the molecular basis for this co-operativity is controversial. One such interaction is the reversal, from inhibition to excitation, at the dopamine D2 receptor in the ghrelin receptors presence, relevant for defecation control. Here we demonstrate that this reversal of dopamine D2 activity, to excitatory, occurs through a dominant switch in downstream signaling. This dominant switch, mediated by downstream signaling, enables fidelity in cellular responses not possible under alternative models, and provides an explanation for previously unresolved observations. Importantly, the switch in D2 signaling does not require ghrelin receptor agonism, rather its constitutive activity, thus accounting for the importance of central nervous system-ghrelin receptor in the absence of endogenous ligands. This re-coding has important implications for our understanding of how atypical receptor pharmacology can occur as well as how sequential signaling at individual neurons may be encoded to produce new outputs.

cell biology↗

bioRxiv2022

Selective transduction and photoinhibition of pre-Botzinger neurons that project to the facial nucleus in rats affect the nasofacial activity

The preBotzinger Complex (preBotC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBotC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBotC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBotC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.

neuroscience↗