Biology subjects

Cody, C. R.

Publications and source records attributed to Cody, C. R..

4 recordsLinked to original sources

bioRxiv2024

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock ("shock response"). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

neuroscience↗

bioRxiv2024

Effects of early life adversity and adolescent basolateral amygdala inhibition on corticolimbic connectivity and anxiety behaviors

Early postnatal development of corticolimbic circuitry is shaped by the environment and is vulnerable to early life challenges. Prior work has shown that early life adversity (ELA) leads to hyperinnervation of glutamatergic basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) in adolescence. While hyperinnervation is associated with later-life anxiety behaviors, the physiological changes underpinning corticolimbic and behavioral impacts of ELA are not understood. We tested whether postsynaptic BLA-driven PFC activity is enhanced in ELA-exposed animals, using the maternal separation (MS) model of ELA. PFC local-field potential following BLA stimulation was facilitated in MS-exposed adolescents. Since ELA increases activity of the early-developing BLA, while the PFC exhibits protracted development, we further examined impacts of glutamatergic BLA activity during early adolescence on later-life PFC innervation and heightened anxiety. In early adolescence, MS-exposed animals exhibited decreased anxiety-like behavior, and acute adolescent BLA inhibition induced behaviors that resembled those of MS animals. To examine long-lasting impacts of adolescent BLA activity on innervation, BLA-originating axonal boutons in the PFC were quantified in late adolescence after early adolescent BLA inhibition. We further tested whether late adolescent BLA-PFC changes were associated with anxious reactivity expressed as heightened acoustic startle responses. MS rearing increased BLA-PFC innervation and threat reactivity in late adolescence, however early adolescent BLA inhibition was insufficient to prevent MS effects, suggesting that earlier BLA activity or post-synaptic receptor rearrangement in the PFC drives altered innervation. Taken together, these findings highlight both pre- and postsynaptic changes in the adolescent BLA-PFC circuit following ELA.

neuroscience↗

bioRxiv2024

An adverse rearing environment alters maternal responsiveness to infant ultrasonic vocalizations

Rodent pups use a variety of ultrasonic vocalizations (USVs) to facilitate maternal care. Importantly, infant USV repertoires are dependent on both the age and early life experiences of the pups. We have shown that an adverse rearing environment modeled with the maternal separation (MS) paradigm alters caregiving behavior, but little is known about how pup USVs differentially elicit maternal attention. In the present study, maternal approach towards a vocalizing pup over a non-vocalizing pup was tested in a Y-maze apparatus at two developmental time points over the course of MS. At the postnatal day (P) 10, dams engaged in longer interaction times with the vocalizing pup compared to the non-vocalizing pup. This effect was modulated by rearing environment and the sex of the pup, with only MS dams spending more time with vocalizing male pups. As expected at P20, dams did not show a preference for either the vocalizing or non-vocalizing pups regardless of rearing environment, however, MS dams spent a greater amount of time in the center of the apparatus as compared to control dams, which can be interpreted as a measure of uncertainty and indecision. These effects are important considering the sex specific effects of MS exposure across all developmental stages. Our novel findings support the hypothesis that sex-specific pup-dam interactions may drive later life outcomes following adversity.

neuroscience↗

bioRxiv2023

Sex-specific adaptations to VTA circuits following subchronic stress

Dysregulation of the mesolimbic reward circuitry is implicated in the pathophysiology of stress-related illnesses such as depression and anxiety. These disorders are more frequently diagnosed in females, and sex differences in the response to stress are likely to be one factor that leads to enhanced vulnerability of females. In this study, we use subchronic variable stress (SCVS), a model in which females are uniquely vulnerable to behavioral disturbances, to investigate sexually divergent mechanisms of regulation of the ventral tegmental area by stress. Using slice electrophysiology, we find that female, but not male mice have a reduction in the ex vivo firing rate of VTA dopaminergic neurons following SCVS. Surprisingly, both male and female animals show an increase in inhibitory tone onto VTA dopaminergic neurons and an increase in the firing rate of VTA GABAergic neurons. In males, however, this is accompanied by a robust increase in excitatory synaptic tone onto VTA dopamine neurons. This supports a model by which SCVS recruits VTA GABA neurons to inhibit dopaminergic neurons in both male and female mice, but males are protected from diminished functioning of the dopaminergic system by a compensatory upregulation of excitatory synapses.

neuroscience↗