Search bioRxiv⌕ Search

Biology subjects

Rodriguez-Romaguera, J.

Publications and source records attributed to Rodriguez-Romaguera, J..

6 recordsLinked to original sources

Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life

BackgroundPupil changes in response to well-controlled stimuli can be used to understand processes that regulate attention, learning, and arousal. This study investigates whether pupil dynamics to social stimuli are associated with concurrent adaptive behavior in typically developing infants. To accomplish this, we developed and assessed pupillary responses to Stimuli for Early Social Arousal and Motivation in Infants (SESAMI). MethodsA sample of forty-six typically developing children aged six to twenty-four months were exposed to SESAMI. Infants were presented with either dynamic social faces or non-social stimuli that controlled for luminance, motion, and auditory exposure. A multi-level mixed effects model was used to fit pupillary response functions (PRFs) that measure the change in pupil size over time as the infants fixate on either a socially dynamic face or a non-social control. This model produces separate social and non-social PRFs for both the population and each individual. An average individual deviation score from the population PRF was calculated separately for social and non-social trials yielding the pupil response index (PRI). Vineland Adaptive Behavior Scales (VABS) were regressed on social and non-social individual PRIs while controlling for age and average fixation time. We tested whether the social PRI was a statistically significant predictor of adaptive behavior by comparing the model predicted VABS scores with observed scores. ResultsAn increase in PRI to social stimuli was significantly associated with better adaptive behaviors in typically developing children between 6 and 24 months of age. ConclusionsSESAMI combined with pupillometry and multi-level mixed effects modeling, provides a novel and scalable framework for quantifying individual differences in pupil changes in response to social stimuli relative to a population-level baseline. By demonstrating that pupil response indices during social fixations predict adaptive behaviors, we lay the foundation to test how these measures may help identify infants with intellectual and developmental disorders.

physiology↗

Social threat alters the behavioral structure of social motivation and reshapes functional brain connectivity

Traumatic social experiences redefine socially motivated behaviors to enhance safety and survival. Although many brain regions have been implicated in signaling a social threat, the mechanisms by which global neural networks regulate such motivated behaviors remain unclear. To address this issue, we first combined traditional and modern behavioral tracking techniques in mice to assess both approach and avoidance, as well as sub-second behavioral changes, during a social threat learning task. We were able to identify previously undescribed body and tail movements during social threat learning and recognition that demonstrate unique alterations into the behavioral structure of social motivation. We then utilized inter-regional correlation analysis of brain activity after a mouse recognizes a social threat to explore functional communication amongst brain regions implicated in social motivation. Broad brain activity changes were observed within the nucleus accumbens, the paraventricular thalamus, the ventromedial hypothalamus, and the nucleus of reuniens. Inter-regional correlation analysis revealed a reshaping of the functional connectivity across the brain when mice recognize a social threat. Altogether, these findings suggest that reshaping of functional brain connectivity may be necessary to alter the behavioral structure of social motivation when a social threat is encountered.

neuroscience↗

The prelimbic prefrontal cortex mediates the development of lasting social phobia as a consequence of social threat conditioning.

Social phobia is highly detrimental for social behavior, mental health, and productivity. Despite much previous research, the behavioral and neurobiological mechanisms associated with the development of social phobia remain elusive. To investigate these issues, the present study implemented a mouse model of social threat conditioning in which mice received electric shock punishment upon interactions with unfamiliar conspecifics. This resulted in immediate reductions in social behavior and robust increases in defensive mechanisms such as avoidance, freezing, darting, and ambivalent stretched posture. Furthermore, social deficits lasted for prolonged periods and were independent of contextual settings, sex variables, or particular identity of the social stimuli. Shedding new light into the neurobiological factors contributing to this phenomenon, we found that optogenetic silencing of the prelimbic (PL), but not the infralimbic (IL), subregion of the medial prefrontal cortex (mPFC) during training led to subsequent forgetting and development of lasting social phobia. Similarly, pharmacological inhibition of NMDARs in PL also impaired the development of social phobia. These findings are consistent with the notion that social-related trauma is a prominent risk factor for the development of social phobia, and that this phenomenon engages learning-related mechanisms within the prelimbic prefrontal cortex to promote prolonged representations of social threat. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/597446v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1f72e5eorg.highwire.dtl.DTLVardef@1053c13org.highwire.dtl.DTLVardef@ab3528org.highwire.dtl.DTLVardef@2ee4d2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Prepronociceptin-expressing neurons in the extended amygdala signal darting away from an aversive odor

Dysregulation in the neural circuitry that encodes physiological arousal responses is thought to contribute to the manifestation of the maladaptive behaviors observed in neuropsychiatric disorders. We previously found that prepronociceptin-expressing neurons in the bed nucleus of the stria terminalis (PnocBNST neurons) modulate rapid changes in physiological arousal upon presentation of motivationally salient stimuli (Rodriguez-Romaguera et al., 2020). However, whether PnocBNST neurons are necessary to regulate behavioral actions to motivationally salient stimuli is still unknown. Here, we investigated the role of PnocBNST neurons in encoding behavioral responses to motivationally salient stimuli using in vivo calcium imaging and optogenetic approaches in freely behaving mice. We find that the bulk activity of PnocBNST neurons increases when mice are near an aversive odor in comparison to a rewarding odor. However, optogenetic inhibition of PnocBNST neurons does not affect the amount of time mice spend near an aversive odor. Further analysis revealed that a subgroup of PnocBNST neurons that correlate with proximity to the aversive odor also correlate to darting away from the same aversive odor. Since these two behaviors are opposite to each other and since we previously found PnocBNST neurons correlate with arousal responses, we believe these results may be due in part to the encoding of arousal responses that occur when mice approach and dart away from aversive stimuli.

neuroscience↗

Prepronociceptin expressing neurons in the extended amygdala encode and promote rapid arousal responses to motivationally salient stimuli

Motivational states are complex and consist of cognitive, emotional, and physiological components controlled by a network across multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identified a subpopulation of neurons within BNST expressing the gene prepronociceptin (PnocBNST), that can modulate the rapid changes in physiological arousal that occur upon exposure to stimuli with motivational salience. Using in vivo two-photon calcium imaging we found that excitatory responses from individual PnocBNST neurons directly corresponded with rapid increases in pupillary size and occurred upon exposure to both aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increased pupillary size, but did not alter approach/avoidance or locomotor behaviors. These findings suggest that excitatory responses in PnocBNST neurons encode rapid arousal responses irrespective of tested behaviors. Further histological, electrophysiological, and single-cell RNA sequencing data revealed that PnocBNST neurons are composed of genetically and anatomically identifiable subpopulations that can be further investigated. Taken together, our findings demonstrate a key role for a PnocBNST neuronal ensemble in encoding the rapid arousal responses that are triggered by motivational stimuli.

neuroscience↗

Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated active avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed initiation of avoidance. However, optogenetic silencing of PL neurons did not delay avoidance. Consistent with this finding, inhibitory, but not excitatory, responses of rostral PL neurons to the tone were correlated with initiation of avoidance. To oppose inhibitory responses, we photoactivated rostral PL neurons during the tone to maintain pre-tone firing rate. Photoactivation of rostral PL (but not caudal PL) neurons at 4 Hz (but not 2 Hz) delayed or prevented avoidance. These findings suggest that the initiation of active avoidance requires inhibitory neuronal responses in rostral PL, and underscores the importance of designing behavioral optogenetic studies based on neuronal firing patterns.

neuroscience↗