Biology subjects

Fry, S. A.

Publications and source records attributed to Fry, S. A..

3 recordsLinked to original sources

bioRxiv2023

Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1

Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.

neuroscience↗

bioRxiv2022

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions

Altered signaling or function of acetylcholine (ACh) has been reported in various neurological diseases, including Alzheimers disease, Tourette syndrome, epilepsy among others. Many neurons that release ACh also co-transmit the neurotransmitter gamma-aminobutyrate (GABA) at synapses in the hippocampus, striatum, and medial prefrontal cortex (mPFC). Although ACh transmission is crucial for higher brain functions such as learning and memory, the role of co-transmitted GABA from ACh neurons in brain function remains unknown. Thus, the overarching goal of this study was to investigate how a systemic loss of GABA co-transmission from ACh neurons affected the behavioral performance of mice. To do this, we used a conditional knock-out mouse of the vesicular GABA transporter (vGAT) crossed with the ChAT-Cre driver line to selectively ablate GABA co-transmission at ACh synapses. In a comprehensive series of standardized behavioral assays, we compared Cre-negative control mice with Cre-positive vGAT knock-out mice of both sexes. Loss of GABA co-transmission from ACh neurons did not disrupt the animals sociability, motor skills or sensation. However, in the absence of GABA co-transmission, we found significant alterations in social, spatial and fear memory as well as a reduced reliance on striatum-dependent response strategies in a T-maze. In addition, male CKO mice showed increased locomotion. Taken together, the loss of GABA co-transmission leads to deficits in higher brain functions and behaviors. Therefore, we propose that ACh/GABA co-transmission modulates neural circuitry involved in the affected behaviors.

neuroscience↗

bioRxiv2019

A role for the locus coeruleus in the modulation of feeding

Recent data suggest that LC-NE neurons play a role in fear-induced suppression of feeding, but their endogenous activity in naturally behaving animals has not been explored. We found that endogenous activity of LC-NE neurons was enhanced during food approach and suppressed during food consumption, and that these food-evoked LC-NE responses were attenuated in sated mice. Interestingly, visual-evoked LC-NE activity was also attenuated in sated mice, demonstrating that internal satiety state modulates LC-NE encoding of multiple behavioral states. We also found that food intake could be attenuated by brief or longer durations of LC-NE activation. Lastly, we demonstrated that activation of LC neurons suppresses feeding and enhances avoidance and anxiety-like responding through a projection to the lateral hypothalamus. Collectively, our data suggest that LC-NE neurons modulate feeding by integrating both external cues (e.g., anxiogenic environmental cues) and internal drives (e.g., nutritional state).

neuroscience↗