Biology subjects

Brenhouse, H. C.

Publications and source records attributed to Brenhouse, H. C..

6 recordsLinked to original sources

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↗

bioRxiv2021

Insular cortex corticotropin-releasing factor integrates stress signaling with social decision making.

Impairments in social cognition manifest in a variety of psychiatric disorders, making the neurobiological mechanisms underlying social decision making of particular translational importance. The insular cortex is consistently implicated in stress-related social and anxiety disorders, which are associated with diminished ability to make and use inferences about the emotions of others to guide behavior. We investigated how corticotropin releasing factor (CRF), a neuromodulator evoked by both self and social stressors, influenced the insula. In acute slices from male and female rats, CRF depolarized insular pyramidal neurons. In males, but not females, CRF suppressed presynaptic GABAergic inhibition leading to greater excitatory synaptic efficacy in a CRF receptor 1 (CRF1) and cannabinoid receptor 1 (CB1) dependent fashion. In males only, insular CRF increased social investigation, and CRF1 and CB1 antagonists interfered with social decision making. To investigate the molecular and cellular basis for the effect of CRF we examined insular CRF1 and CB1 mRNAs and found greater total insula CRF1 mRNA in females but greater CRF1 and CB1 mRNA colocalization in male insular cortex glutamatergic neurons which suggest complex, sex-specific organization of CRF and endocannabinoid systems. Together these results reveal a new sex-specific mechanism by which stress and affect contribute to social decision making.

neuroscience↗

bioRxiv2020

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Adversity early in life substantially impacts prefrontal cortex (PFC) development and vulnerability to later-life psychopathology. Importantly, repeated adverse experiences throughout childhood increase the risk for PFC-mediated behavioral deficits more commonly in women. Evidence from animal models points to effects of adversity on later-life neural and behavioral dysfunction; however, few studies have investigated the neurobiological underpinnings of sex-specific, long term consequences of multiple developmental stressors. We modeled early life adversity in rats via maternal separation (postnatal day (P)2-20) and juvenile social isolation (P21-35). Adult (P85) male and female rats were assessed for differences in the presence and structural integrity of PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons. PNNs are extracellular matrix structures formed during critical periods in postnatal development that play a key role in the plasticity of PV cells. Females - but not males - exposed to multiple hits of adversity demonstrated a reduction in PFC PV cells in adulthood. We also observed a sex-specific, potentiated reduction in PV+ PNN structural integrity. Moreover, correlations between neural disruption and hyperactivity/risk-assessment behavior were altered by adversity differently in males and females. These findings suggest a sex-specific impact of repeated adversity on neurostructural development and implicate PNNs as a contributor to associated behavioral dysfunction.

neuroscience↗

bioRxiv2019

Too much, too young? Altered corticolimbic axonal innervation and resting state functional connectivity suggests sex-dependent outcomes in a rat model of early life adversity

Adverse early experiences significantly alter behavioral and neural trajectories via aberrant brain maturation. Children with a history of early life stress (ELS) exhibit maladaptive behaviors and increased risk of mental illness later in life. Evidence in ELS-exposed humans identifies a role of atypical corticolimbic development; specifically, within amygdala-prefrontal cortex (PFC) circuits, and show precocially mature task-based corticolimbic functional connectivity (FC). However, the neurobiological substrates of such ELS-driven developmental changes remain unknown. Here, we identify putative neurobiological changes to determine the timeline of developmental perturbations following ELS in rats. Anterograde axonal tracing from basolateral amygdala (BLA) to pre- and infralimbic (PL, IL) PFC was quantified at postnatal days (PD)28, 38, and 48, along with anxiety-like behavior, in maternally separated (ELS) or control reared (CON) male and female rats. Resting state (rs)FC was assessed at PD28 and PD48 in a separate cohort. We report that ELS-exposed female rats show early maturation of BLA-PFC innervation at PD28, with ELS-related changes in males not appearing until PD38. ELS disrupted the maturation of rsFC from PD28 to PD48 in females, with enduring relationships between early rsFC and later anxiety-like behavior. Only transient ELS-related changes in rsFC were seen in male PL. Together, these data provide evidence that female rats may be more vulnerable to the effects of ELS via precocial BLA-PFC innervation, which may drive altered corticolimbic rsFC. These data also provide evidence that increased BLA-IL rsFC is associated with behavioral resiliency following ELS in female rats, providing mechanistic insight into the underlying etiology of adversity-induced vulnerability and resiliency.

neuroscience↗

bioRxiv2018

22kHz and 55kHz ultrasonic vocalizations differentially influence neural and behavioral outcomes: Implications for modeling anxiety via auditory stimuli in the rat

The communicative role of ultrasonic vocalizations (USVs) in rodents is well established, with distinct USVs indicative of different affective states. USVs in the 22kHz range are typically emitted by adult rats when in anxiety-or fear-provoking situations (e.g. predator odor, social defeat), while 55kHz range USVs are emitted in appetitive situations (e.g., play, anticipation of reward). Previous work indicates that USVs (real-time and playback) can effectively communicate these affective states and influence changes in behavior and neural activity of the receiver. Changes in cFos activation following 22kHz USVs have been seen in cortical and limbic regions involved in anxiety, including the basolateral amygdala (BLA). However, it is unknown how USV playback influences cFos activity within the basal nucleus of the stria terminalis (BNST), a region also thought to be critical in processing anxiety-related information. The present work sought to characterize distinct behavioral, physiological, and neural responses in rats presented with aversive (22kHz) compared to appetitive (55kHz) USVs or silence. Our findings show that rats exposed to 22kHz USVs: 1) engage in anxiety-like behaviors in the open field and elevated zero maze, and 2) show distinct patterns of cFos activation within the BLA and BNST that contrast those seen in 55kHz playback. Specifically, 22kHz USVs increased cFos density in the anterodorsal nuclei, while 55kHz playback increased cFos in the oval nucleus of the BNST. These results provide important groundwork for leveraging ethologically-relevant stimuli in the rat to improve our understanding of anxiety-related responses in both typical and pathological populations.

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