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Tschida, K.

Publications and source records attributed to Tschida, K..

7 recordsLinked to original sources

The infralimbic, but not the prelimbic cortex is needed for a complex olfactory memory task.

The medial prefrontal cortex (mPFC) plays a key role in memory and behavioral flexibility, and a growing body of evidence suggests that the prelimbic (PL) and infralimbic (IL) subregions contribute differently to these processes. Studies of fear conditioning and goal-directed learning suggest that the PL promotes behavioral responses and memory retrieval, while the IL inhibits them. Other studies have shown that the mPFC is engaged under conditions of high interference. This raises the possibility that the PL and IL play differing roles in resolving interference. To examine this, we first used chemogenetics (DREADDs) to suppress mPFC neuronal activity and tested subjects on a conditional discrimination task known to be sensitive to muscimol inactivation. After confirming the effectiveness of the DREADD procedures, we conducted a second experiment to examine the PL and IL roles in a high interference memory task. We trained rats on two consecutive sets of conflicting odor discrimination problems, A and B, followed by test sessions involving a mid-session switch between the problem sets. Controls repeatedly performed worse on Set A, suggesting that learning Set B inhibited the rats ability to retrieve Set A memories (i.e. retroactive interference). PL inactivation rats performed similarly to controls. However, IL inactivation rats did not show this effect, suggesting that the IL plays a critical role in suppressing the retrieval of previously acquired memories that may interfere with retrieval of more recent memories. These results suggest that the IL plays a critical role in memory control processes needed for resolving interference.

neuroscience↗

Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner

Social animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3-day) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POAsocial neurons) but not in single-housed females that did not engage in social interactions. TRAP2-mediated chemogenetic silencing of POAsocial neurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation, USV production, and mounting. In contrast, caspase-mediated ablation of POAsocial neurons in single-housed females robustly attenuates mounting but does not decrease social investigation or USV production. Optogenetic activation of POAsocial neurons in group-housed females promotes social investigation and USV production but does not recapitulate the effects of short-term isolation on mounting. To understand whether a similar population of POAsocial neurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions. Chemogenetic silencing of POAsocial neurons in single-housed males during interactions with females reduces mounting but does not affect social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner.

neuroscience↗

Different populations of midbrain neurons control the production of distinct acoustic categories of vocalization

Animals produce different acoustic types of vocalizations in different behavioral contexts. The midbrain periaqueductal gray (PAG) is obligatory for vocal production (Jurgens, 1994, 2002, 2009), but how midbrain circuits are organized to control the production of different vocalization types remains unknown. To test whether a single population of midbrain neurons regulates the production of different vocalization types, we applied intersectional methods to selectively ablate a population of midbrain neurons required for the production of ultrasonic vocalizations (USVs) in mice. We find that although ablation of these PAG-USV neurons blocks USV production in both males and females, these neurons are not required for the production of squeaks. Our findings provide strong evidence that distinct populations of midbrain neurons control the production of different acoustic categories of vocalizations.

neuroscience↗

Rates but not acoustic features of ultrasonic vocalizations are related to non-vocal behaviors in mouse pups

Mouse pups produce ultrasonic vocalizations (USVs) in response to isolation from the nest (i.e., isolation USVs). Rates and acoustic features of isolation USVs change dramatically over the first two weeks of life, and there is also substantial variability in the rates and acoustic features of isolation USVs at a given postnatal age. The factors that contribute to within-age variability in isolation USVs remain largely unknown. Here, we explore the extent to which non-vocal behaviors of mouse pups relate to the within-age variability in rates and acoustic features of their USVs. We recorded non-vocal behaviors of isolated C57BL/6J mouse pups at four postnatal ages (postnatal days 5, 10, 15, and 20), measured rates of isolation USV production, and applied a combination of hand-picked acoustic feature measurements and an unsupervised machine learning-based vocal analysis method to examine USV acoustic features. When we considered different categories of non-vocal behavior, our analyses revealed that mice in all postnatal age groups produce higher rates of isolation USVs during active non-vocal behaviors than when lying still. Moreover, rates of isolation USVs are correlated with the intensity (i.e., magnitude) of non-vocal body and limb movements within a given trial. In contrast, USVs produced during different categories of non-vocal behaviors and during different intensities of non-vocal movement do not differ substantially in their acoustic features. Our findings suggest that levels of behavioral arousal contribute to within-age variability in rates, but not acoustic features, of mouse isolation USVs.

animal behavior and cognition↗

Sex- and context-dependent effects of acute isolation on vocal and non-vocal social behaviors in mice

Humans are extraordinarily social, and social isolation has profound effects on our behavior, ranging from increased social motivation following short periods of social isolation to increased anti-social behaviors following long-term social isolation. Mice are frequently used as a model to understand how social isolation impacts the brain and behavior. While the effects of chronic social isolation on mouse social behavior have been well studied, much less is known about how acute isolation impacts mouse social behavior and whether these effects vary according to the sex of the mouse and the behavioral context of the social encounter. To address these questions, we characterized the effects of acute (3-day) social isolation on the vocal and non-vocal social behaviors of male and female mice during same-sex and opposite-sex social interactions. Our experiments uncovered pronounced effects of acute isolation on social interactions between female mice, while revealing more subtle effects on the social behaviors of male mice during same-sex and opposite-sex interactions. Our findings advance the study of same-sex interactions between female mice as an attractive paradigm to investigate neural mechanisms through which acute isolation enhances social motivation and promotes social behavior.

animal behavior and cognition↗

Circuit and synaptic organization of forebrain-to-midbrain pathways that promote and suppress vocalization

Animals vocalize only in certain behavioral contexts, but the circuits and synapses through which forebrain neurons trigger or suppress vocalization remain unknown. Here we used transsynaptic tracing to identify two populations of inhibitory neurons that lie upstream of neurons in the periaqueductal gray that gate the production of ultrasonic vocalizations in mice (i.e., PAG-USV neurons). Activating PAG-projecting neurons in the preoptic hypothalamus (POAPAG neurons) elicited USV production in the absence of social cues. In contrast, activating PAG-projecting neurons in the central-medial boundary zone of the amygdala (AmgC/M-PAG neurons) transiently suppressed USV production without disrupting non-vocal social behavior. Optogenetics-assisted circuit mapping in brain slices revealed that POAPAG neurons directly inhibit PAG interneurons, which in turn inhibit PAG-USV neurons, whereas AmgC/M-PAG neurons directly inhibit PAG-USV neurons. These experiments identify two major forebrain inputs to the PAG that trigger and suppress vocalization, respectively, while also establishing the synaptic mechanisms through which these neurons exert opposing behavioral effects.

neuroscience↗

Identification of midbrain neurons essential for vocal communication

Vocalizations are an essential medium for communication and courtship in numerous mammalian species ranging from mice to humans. In mammals, the midbrain PAG serves as an obligatory node in a vocalization-related network that spans the forebrain and brainstem1-3, as bilateral lesions of the PAG result in mutism2-5. Despite the PAGs importance for vocal production, the identity, function, and connectivity of PAG neurons involved in vocalization has remained elusive, in part because the PAG is a functionally and anatomically heterogeneous structure that serves myriad roles including nociception, defensive behaviors, and autonomic regulation6-9. Here we used a viral genetic \"tagging\" method10,11 to identify a distinct subset of PAG neurons in the male mouse that are selectively activated during the production of ultrasonic vocalizations (USVs) elicited by female cues. Silencing these PAG-USV neurons rendered males mute without affecting their other courtship behaviors and also impaired their ability to attract female mice in a social choice assay. Activating these neurons using chemogenetic or optogenetic methods strongly elevated USV production, even in the absence of female cues. Notably, the timing of individual USVs was entrained to the expiratory phase of breathing but not to the pattern of optogenetic stimulation, suggesting that PAG-USV neural activity initiates and sets the duration of vocal bouts and recruits downstream premotor circuits that precisely pattern vocal output. Consistent with this idea, we found that PAG-USV neurons extend axons into pontine and medullary regions that are speculated to contain premotor central pattern generators important for vocalization3,12,13. These experiments establish the identity of the PAG neurons selectively required for USV production in mice, map their efferent connections, and demonstrate the communicative salience of male USVs in promoting female social affiliation.

neuroscience↗