Biology subjects

Barson, J. R.

Publications and source records attributed to Barson, J. R..

4 recordsLinked to original sources

bioRxiv2025

Depression-like behavior following mild traumatic brain injury in adolescent rats: a role for limbic neuropeptides

Mild traumatic brain injury (mTBI) is common among adolescents because of their participation in contact sports and mTBI is more likely to lead to depression-related behaviors in girls than boys. Various neuropeptides, often within the limbic system, have been implicated in the regulation of depression-related behaviors. To identify potential neuropeptide involvement in behavioral effects of mTBI, this study used adolescent-age male and female rats to compare the effects of single and repetitive mTBI on depression-like behavior and limbic neuropeptide expression. Female but not male rats displayed increased immobility in the forced swim test compared to sham-injured rats at 5-weeks (chronic), but not 2-weeks (acute) following closed-head injury, and this effect was estrous cycle-dependent following single but not repetitive injury. In the nucleus accumbens (NAc), a major limbic nucleus, mRNA expression of corticotropin-releasing factor (CRF) and dynorphin (DYN) was decreased after single injury only in female rats, particularly during the estrus phase, while expression of enkephalin (ENK) was decreased after repetitive injury. In the paraventricular nucleus of the thalamus (PVT), another limbic nucleus, mRNA expression of pituitary adenylate cyclase-activating polypeptide (PACAP) was increased in repetitively injured female but not male rats at 2- and 5-weeks but was unchanged in single injured female rats compared to sham-injured rats. These data suggest that depression-like behavior emerges in the chronic phase following adolescent mTBI only in females, being estrous cycle-dependent following single-injury. Moreover, reduced ENK in the NAc and elevated PACAP in the PVT may contribute to depression-like behavior in females following repetitive mTBI.

neuroscience↗

bioRxiv2025

Subcellular interactions of neuropeptide Y and corticotropin-releasing factor in the central nucleus of the amygdala in the mouse

Neuropeptide Y (NPY) is ubiquitously distributed throughout the central nervous system. Recognized as a mediator of stress resilience, NPY has been shown to counteract the excitatory effects of the neuropeptide corticotropin-releasing factor (CRF), that orchestrates the stress response. In the mouse, while NPY and CRF exhibit a high degree of neuroanatomical association in the central nucleus of the amygdala (CeA) indicating potential significant interactions, the synaptic organizations of these neuropeptides have not been elucidated. In the present study, we determined the interactions between NPY and CRF in the CeA. Immunofluorescence microscopy presented that NPY-immunoreactive varicose processes were distributed throughout the CeA and contacted CRF-containing neurons. Using electron microscopy, immunoperoxidase labeling for NPY and gold-silver labeling for CRF showed that NPY-labeled axon terminals (NPY-t) form synapses with CRF-labeled dendrites (CRF-d). Semi-quantitative analysis revealed that 163 of NPY-t directly target CRF-d. In addition, approximately 85% of NPY-t form symmetric synapses with CRF-d while approximately 1% form asymmetric synapses. These findings provide the first ultrastructural evidence that NPY-containing axon terminals make direct contact with CRF-containing dendrites in the CeA. This suggests that the CRF-containing neurons in the CeA may be a key site for NPY action, potentially influencing brain regions involved in stress responses and stress-related psychiatric disorders, and alcohol use disorders.

neuroscience↗

bioRxiv2024

Pituitary adenylate cyclase-activating polypeptide (PACAP) overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats

BackgroundPituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored. MethodsAdult, female Long-Evans rats were injected in the PVT with an AAV to increase expression of PACAP or a control AAV. They were then investigated for subsequent gene and peptide levels of PACAP in the PVT; ethanol drinking and preference; sucrose drinking and preference; or locomotor activity in a novel chamber, behavior in a light-dark box, behavior in a novelty suppression of feeding test, locomotor activity in a familiar activity chamber, and behavior in a forced swim test. ResultsGene expression of PACAP was significantly increased in the PVT by four weeks after injection with the PACAP AAV, and this resulted in a specific increase in levels of PACAP-27. Rats injected with the PACAP AAV demonstrated reduced drinking and preference for ethanol under the intermittent-access procedure compared to those injected with the control AAV. In contrast, rats injected with the PACAP AAV showed no significant difference in drinking or preference for sucrose, or in any affective behavior tested, except that they spent less time swimming in the forced swim test. ConclusionsIn light of the low overall level of expression of PACAP-27 in the brain, the ability of PACAP-27 in the PVT to control ethanol drinking, with minimal effects on other motivated or affective behaviors, supports the idea that compounds related to PACAP-27 should be investigated as potential therapeutics for the treatment of alcohol use disorder.

neuroscience↗

bioRxiv2020

Kappa-opioid receptor stimulation in the nucleus accumbens shell: Differential effects across the rostro-caudal axis on dopamine transmission and affective behavior

Neural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behavior, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behavior using approach-avoidance assays. We report here that activation of KORs in the caudal NAc shell significantly inhibits dopamine release, stimulates novelty-induced rearing behavior, increases avoidance behavior, and reduces locomotor activity. In contrast, activation of KORs in the rostral NAc shell inhibits dopamine release to a lesser extent and instead increases approach behavior. Taken together, these results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and they suggest that this might be due to differences in KOR control over dopamine release.

neuroscience↗