Biology subjects

Laine, M. A.

Publications and source records attributed to Laine, M. A..

3 recordsLinked to original sources

bioRxiv2023

CB1R blockade unmasks TRPV1-mediated contextual fear generalization in female, but not male rats

Increasing evidence suggests that the neurobiological processes that govern learning and memory can be different in males and females, and here we asked specifically whether the endocannabinoid (eCB) system could modulate Pavlovian fear conditioning in a sex-dependent manner. Systemic (i.p.) injection of CB1R antagonist AM251 in adult male and female Sprague Dawley rats prior to auditory cued fear conditioning produced a female-specific increase in freezing that persisted across extinction and extinction retrieval tests but was prevented by co-administration of TRPV1R antagonist Capsazepine. Notably, AM251 also produced robust freezing in a novel context prior to auditory cue presentation the day following drug administration, but not the day of, suggesting that CB1R blockade elicited contextual fear generalization in females. To identify a potential synaptic mechanism for these sex differences, we next used liquid chromatography/tandem mass spectrometry, Western Blot, and confocal-assisted immunofluorescence techniques to quantify anandamide (AEA), TRPV1R, and perisomatic CB1R expression, respectively, focusing on the ventral hippocampus (vHip). Fear conditioning elicited increased vHip AEA levels in females only, and in both sexes, CB1R expression around vHip efferents targeting the basolateral amygdala (BLA) was twice that at neighboring vHip neurons. Finally, quantification of the vHip-BLA projections themselves revealed that females have over twice the number of neurons in this pathway that males do. Together, our data support a model in which sexual dimorphism in vHip-BLA circuitry promotes a female-specific dependence on CB1Rs for context processing that is sensitive to TRPV1-mediated disruption when CB1Rs are blocked.

neuroscience↗

bioRxiv2022

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

Pavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction and assess the relationship between different threat-related behaviors. To probe the effects of aversive stimulus intensity, we exposed the rats to mild (0.3 mA), moderate (0.5 mA) or strong (1 mA) foot shocks. We found that males consistently emitted more alarm calls than females, and male alarm calls were more closely contingent on shock intensity than were female alarm calls. Furthermore, 25 % of males and 45 % of females did not emit alarm calls. Males that made alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female alarm callers and non-callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. Some rats continued to alarm-call during extinction learning (90% of males, 30% of females) and retrieval (65% of males, 20% of females). Collectively these data suggest sex-dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion. Significance statementBehavioral neuroscientists can access various outputs during behavioral tests to draw conclusions about internal states of animals. While freezing is the most common index of rodents feeling threatened, these animals also emit specific ultrasonic vocalizations during aversive situations. Here we record several motor and vocal behaviors to assess how they relate to each other as threat responses, and how such relationships vary across sex. We found robust differences in how much male and female rats engaged in so-called alarm vocalizations. These vocalizations were subject to extinction in both sexes, but correlated with freezing only in males. As the field advances to include more females in preclinical research, it is crucial that we understand how similar-appearing outputs may reflect sex-biased features.

animal behavior and cognition↗

bioRxiv2022

Mind the gap: Nodes of Ranvier are remodeled by chronic psychosocial stress and neuronal activity

Differential expression of myelin-related genes and changes in myelin thickness have been demonstrated in mice after chronic psychosocial stress, a risk factor for anxiety disorders. To determine whether and how stress affects structural remodeling of nodes of Ranvier, another form of myelin plasticity, we developed a 3D reconstruction analysis of node morphology in C57BL/6NCrl and DBA/2NCrl mice. We identified strain-dependent effects of chronic stress on node morphology, including elongation of paranodes in the medial prefrontal cortex (mPFC) in DBA/2NCrl mice. Furthermore, chronic chemogenetic activation of the ventral hippocampus-to-mPFC pathway resulted in increased risk assessment behavior and shortened paranodes specifically in stimulated axons, providing a direct link between anxiety-like behavior and remodeling of the nodes. Altogether, our data demonstrate genetic regulation of nodal remodeling in stress and suggest an activity-dependent regulation of paranodes in anxiety-related circuits. Nodal remodeling may thus contribute to the aberrant circuit function associated with anxiety disorders.

neuroscience↗