Predictive Mouse Ultrasonic Vocalization Sequences: Uncovering Behavioral Significance, Auditory Cortex Neuronal Preferences, and Social-Experience-Driven Plasticity.

Mouse ultrasonic vocalizations (USVs) contain predictable sequential structures like bird songs and speech. Neural representation of USVs in the mouse primary auditory cortex (Au1) and its plasticity with experience has been largely studied with single-syllables or dyads, without using the predictability in USV sequences. Studies using playback of USV sequences have used randomly selected sequences from numerous possibilities. The current study uses mutual information to obtain context-specific natural sequences (NSeqs) of USV syllables capturing the observed predictability in male USVs in different contexts of social interaction with females. Behavioral and physiological significance of NSeqs over random sequences (RSeqs) lacking predictability were examined. Female mice, never having the social experience of being exposed to males, showed higher selectivity for NSeqs behaviorally and at cellular levels probed by expression of immediate early gene c-fos in Au1. The Au1 supragranular single units also showed higher selectivity to NSeqs over RSeqs. Social-experience-driven plasticity in encoding NSeqs and RSeqs in adult females was probed by examining neural selectivities to the same sequences before and after the above social experience. Single units showed enhanced selectivity for NSeqs over RSeqs after the social experience. Further, using two-photon Ca2+ imaging, we observed social experience-dependent changes in the selectivity of sequences of excitatory and somatostatin-positive inhibitory neurons but not parvalbumin-positive inhibitory neurons of Au1. Using optogenetics, somatostatin-positive neurons were identified as a possible mediator of the observed social-experience-driven plasticity. Our study uncovers the importance of predictive sequences and introduces mouse USVs as a promising model to study context-dependent speech like communications.SIGNIFICANCE STATEMENT Humans need to detect patterns in the sensory world. For instance, speech is meaningful sequences of acoustic tokens easily differentiated from random ordered tokens. The structure derives from the predictability of the tokens. Similarly, mouse vocalization sequences have predictability and undergo context-dependent modulation. Our work investigated whether mice differentiate such informative predictable sequences (NSeqs) of communicative significance from RSeqs at the behavioral, molecular, and neuronal levels. Following a social experience in which NSeqs occur as a crucial component, mouse auditory cortical neurons become more sensitive to differences between NSeqs and RSeqs, although preference for individual tokens is unchanged. Thus, speech-like communication and its dysfunction may be studied in circuit, cellular, and molecular levels in mice.

Social play behavior shapes the development of prefrontal inhibition in a region-specific manner.

Experience-dependent organization of neuronal connectivity is critical for brain development. We recently demonstrated the importance of social play behavior for the developmental fine-tuning of inhibitory synapses in the medial prefrontal cortex in rats. When these effects of play experience occur and if this happens uniformly throughout the prefrontal cortex is currently unclear. Here we report important temporal and regional heterogeneity in the impact of social play on the development of excitatory and inhibitory neurotransmission in the medial prefrontal cortex and the orbitofrontal cortex. We recorded in layer 5 pyramidal neurons from juvenile (postnatal day (P)21), adolescent (P42), and adult (P85) rats after social play deprivation (between P21 and P42). The development of these prefrontal cortex subregions followed different trajectories. On P21, inhibitory and excitatory synaptic input was higher in the orbitofrontal cortex than in the medial prefrontal cortex. Social play deprivation did not affect excitatory currents, but reduced inhibitory transmission in both medial prefrontal cortex and orbitofrontal cortex. Intriguingly, the reduction occurred in the medial prefrontal cortex during social play deprivation, whereas the reduction in the orbitofrontal cortex only became manifested after social play deprivation. These data reveal a complex interaction between social play experience and the specific developmental trajectories of prefrontal subregions.

Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats.

Sensory driven activity during early life is critical for setting up the proper connectivity of the sensory cortices. We ask here whether social play behavior, a particular form of social interaction that is highly abundant during postweaning development, is equally important for setting up connections in the developing prefrontal cortex (PFC). Young male rats were deprived from social play with peers during the period in life when social play behavior normally peaks [postnatal day 21-42] (SPD rats), followed by resocialization until adulthood. We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected. This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells. In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning (PRL) task, which depends on the integrity of the PFC, by using a more simplified cognitive strategy than controls. Interestingly, we observed that one daily hour of play during SPD partially rescued the behavioral performance in the PRL, but did not prevent the decrease in PFC inhibitory synaptic inputs. Our data demonstrate the importance of unrestricted social play for the development of inhibitory synapses in the PFC and cognitive skills in adulthood and show that specific synaptic alterations in the PFC can result in a complex behavioral outcome.SIGNIFICANCE STATEMENT This study addressed the question whether social play behavior in juvenile rats contributes to functional development of the prefrontal cortex (PFC). We found that rats that had been deprived from juvenile social play (social play deprivation - SPD) showed a reduction in inhibitory synapses in the PFC and a simplified strategy to solve a complex behavioral task in adulthood. Providing one daily hour of play during SPD partially rescued the cognitive skills in these rats, but did not prevent the reduction in PFC inhibitory synapses. Our results demonstrate a key role for unrestricted juvenile social play in PFC development and emphasize the complex relation between PFC circuit connectivity and cognitive function.

Neurobiological predispositions for musicality: White matter in infancy predicts school-age music aptitude.

Musical training has long been viewed as a model for experience-dependent brain plasticity. Reports of musical training-induced brain plasticity are largely based on cross-sectional studies comparing musicians to non-musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre-existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school-age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract in infancy is associated with school-age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter-hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build. RESEARCH HIGHLIGHTS: Structural organization of the right corticospinal tract in infancy is associated with school-age musical aptitude skills. Longitudinal associations between the right corticospinal tract in infancy and school-age rhythmic music aptitude skills remain significant even when controlling for language ability. Findings support the notion of predispositions for success in music, and suggest that musical predispositions likely build upon a neural structural scaffold established in infancy. Findings support the working hypothesis that a dynamic interaction between predisposition and experience established in infancy shape the trajectory of long-term musical development.

Neuronal Oscillatory Signatures in the Developing Mouse Visual Cortex After Short-Term Monocular Deprivation.

Development and maturation in cortical networks depend on neuronal activity. For stabilization and pruning of connections, synchronized oscillations play a crucial role. A fundamental mechanism that enables coordinated activity during brain functioning is formed of synchronized neuronal oscillations in low- (delta and theta) and high- (gamma) frequency bands. The relationship between neural synchrony, cognition, and the perceptual process has been widely studied, but any possible role of neural synchrony in amblyopia has been less explored. We hypothesized that monocular deprivation (MD) during early postnatal life would lead to changes in neuronal activity that would be demonstrated by changes in phase-amplitude coupling (PAC) and altered power in specific oscillatory frequency. Our results demonstrate that functional connectivity in the visual cortex is altered by MD during adolescence. The amplitude of high-frequency oscillations is modulated by the phase of low-frequency oscillations. Demonstration of enhanced delta-gamma and theta-gamma PAC indicates that our results are relevant for a broad range of nested oscillatory markers. These markers are inherent to neuronal processing and are consistent with the hypothesized increase in the intrinsic coupling that arises from neural oscillatory phase alignment. Our results reveal distinct frequency bands exhibit altered power and coherence variations modulated by experience-driven plasticity.

Remodelling of myelinated axons and oligodendrocyte differentiation is stimulated by environmental enrichment in the young adult brain.

Oligodendrocyte production and myelination continues lifelong in the central nervous system (CNS), and all stages of this process can be adaptively regulated by neuronal activity. While artificial exogenous stimulation of neuronal circuits greatly enhances oligodendrocyte progenitor cell (OPC) production and increases myelination during development, the extent to which physiological stimuli replicates this is unclear, particularly in the adult CNS when the rate of new myelin addition slows. Here, we used environmental enrichment (EE) to physiologically stimulate neuronal activity for 6 weeks in 9-week-old C57BL/six male and female mice and found no increase in compact myelin in the corpus callosum or somatosensory cortex. Instead, we observed a global increase in callosal axon diameter with thicker myelin sheaths, elongated paranodes and shortened nodes of Ranvier. These findings indicate that EE induced the dynamic structural remodelling of myelinated axons. Additionally, we observed a global increase in the differentiation of OPCs and pre-myelinating oligodendroglia in the corpus callosum and somatosensory cortex. Our findings of structural remodelling of myelinated axons in response to physiological neural stimuli during young adulthood provide important insights in understanding experience-dependent myelin plasticity throughout the lifespan and provide a platform to investigate axon-myelin interactions in a physiologically relevant context.

Early Visual Motion Experience Improves Retinal Encoding of Motion Directions.

Altered sensory experience in early life often leads to altered response properties of the sensory neurons. This process is mostly thought to happen in the brain, not in the sensory organs. We show that in the mouse retina of both sexes, exposed to a motion-dominated visual environment from eye-opening, the ON-OFF direction selective ganglion cells (ooDSGCs) develop significantly stronger direction encoding ability for motion in all directions. This improvement occurs independent of the motion direction used for training. We demonstrated that this enhanced ability to encode motion direction is mainly attributed to increased response reliability of ooDSGCs. Closer examination revealed that the excitatory inputs from the ON bipolar pathway showed enhanced response reliability after the motion experience training, while other synaptic inputs remain relatively unchanged. Our results demonstrate that retina adapts to the visual environment during neonatal development.SIGNIFICANCE STATEMENT We found that retina, as the first stage of visual sensation, can also be affected by experience dependent plasticity during development. Exposure to a motion enriched visual environment immediately after eye-opening greatly improves motion direction encoding by direction selective retinal ganglion cells (RGCs). These results motivate future studies aimed at understanding how visual experience shapes the retinal circuits and the response properties of retinal neurons.

Dual-Component Structural Plasticity Mediated by αCaMKII Autophosphorylation on Basal Dendrites of Cortical Layer 2/3 Neurones.

Sensory cortex exhibits receptive field plasticity throughout life in response to changes in sensory experience and offers the experimental possibility of aligning functional changes in receptive field properties with underpinning structural changes in synapses. We looked at the effects on structural plasticity of two different patterns of whisker deprivation in male and female mice: chessboard deprivation, which causes functional plasticity; and all deprived, which does not. Using 2-photon microscopy and chronic imaging through a cranial window over the barrel cortex, we found that layer 2/3 neurones exhibit robust structural plasticity, but only in response to whisker deprivation patterns that cause functional plasticity. Chessboard pattern deprivation caused dual-component plasticity in layer 2/3 by (1) increasing production of new spines that subsequently persisted for weeks and (2) enlarging spine head sizes in the preexisting stable spine population. Structural plasticity occurred on basal dendrites, but not apical dendrites. Both components of plasticity were absent in αCaMKII-T286A mutants that lack LTP and experience-dependent potentiation in barrel cortex, implying that αCaMKII autophosphorylation is not only important for stabilization and enlargement of spines, but also for new spine production. These studies therefore reveal the relationship between spared whisker potentiation in layer 2/3 neurones and the form and mechanisms of structural plasticity processes that underlie them.SIGNIFICANCE STATEMENT This study provides a missing link in a chain of reasoning that connects LTP to experience-dependent functional plasticity in vivo We found that increases in dendritic spine formation and spine enlargement (both of which are characteristic of LTP) only occurred in barrel cortex during sensory deprivation that produced potentiation of sensory responses. Furthermore, the dendritic spine plasticity did not occur during sensory deprivation in mice lacking LTP and experience-dependent potentiation (αCaMKII autophosphorylation mutants). We also found that the dual-component dendritic spine plasticity only occurred on basal dendrites and not on apical dendrites, thereby resolving a paradox in the literature suggesting that layer 2/3 neurones lack structural plasticity in response to sensory deprivation.

Inherent auditory skills rather than formal music training shape the neural encoding of speech.

Musical training is associated with a myriad of neuroplastic changes in the brain, including more robust and efficient neural processing of clean and degraded speech signals at brainstem and cortical levels. These assumptions stem largely from cross-sectional studies between musicians and nonmusicians which cannot address whether training itself is sufficient to induce physiological changes or whether preexisting superiority in auditory function before training predisposes individuals to pursue musical interests and appear to have similar neuroplastic benefits as musicians. Here, we recorded neuroelectric brain activity to clear and noise-degraded speech sounds in individuals without formal music training but who differed in their receptive musical perceptual abilities as assessed objectively via the Profile of Music Perception Skills. We found that listeners with naturally more adept listening skills ("musical sleepers") had enhanced frequency-following responses to speech that were also more resilient to the detrimental effects of noise, consistent with the increased fidelity of speech encoding and speech-in-noise benefits observed previously in highly trained musicians. Further comparisons between these musical sleepers and actual trained musicians suggested that experience provides an additional boost to the neural encoding and perception of speech. Collectively, our findings suggest that the auditory neuroplasticity of music engagement likely involves a layering of both preexisting (nature) and experience-driven (nurture) factors in complex sound processing. In the absence of formal training, individuals with intrinsically proficient auditory systems can exhibit musician-like auditory function that can be further shaped in an experience-dependent manner.

Experience-dependent mechanisms in the regulation of parental care.

Maternal behavior is a defining characteristic of mammals, which is regulated by a core, conserved neural circuit. However, mothering behavior is not always a default response to infant conspecifics. For example, initial fearful, fragmented or aggressive responses toward infants in laboratory rats and mice can give way to highly motivated and organized caregiving behaviors following appropriate hormone exposure or repeated experience with infants. Therefore hormonal and/or experiential factors must be involved in determining the extent to which infants access central approach and avoidance neural systems. In this review we describe evidence supporting the idea that infant conspecifics are capable of activating distinct neural pathways to elicit avoidant, aggressive and parental responses from adult rodents. Additionally, we discuss the hypothesis that alterations in transcriptional regulation within the medial preoptic area of the hypothalamus may be a key mechanism of neural plasticity involved in programming the differential sensitivity of these neural pathways.

Experience-dependent tuning of early olfactory processing in the adult honey bee, Apis mellifera.

Experience-dependent plasticity in the central nervous system allows an animal to adapt its responses to stimuli over different time scales. In this study, we explored the impacts of adult foraging experience on early olfactory processing by comparing naturally foraging honey bees, Apis mellifera, with those that experienced a chronic reduction in adult foraging experience. We placed age-matched sets of sister honey bees into two different olfactory conditions, in which animals were allowed to forage ad libitum In one condition, we restricted foraging experience by placing honey bees in a tent in which both sucrose and pollen resources were associated with a single odor. In the second condition, honey bees were allowed to forage freely and therefore encounter a diversity of naturally occurring resource-associated olfactory experiences. We found that honey bees with restricted foraging experiences had altered antennal lobe development. We measured the glomerular responses to odors using calcium imaging in the antennal lobe, and found that natural olfactory experience also enhanced the inter-individual variation in glomerular response profiles to odors. Additionally, we found that honey bees with adult restricted foraging experience did not distinguish relevant components of an odor mixture in a behavioral assay as did their freely foraging siblings. This study highlights the impacts of individual experience on early olfactory processing at multiple levels.

Disrupted AMPA Receptor Function upon Genetic- or Antibody-Mediated Loss of Autism-Associated CASPR2.

Neuropsychiatric disorders share susceptibility genes, suggesting a common origin. One such gene is CNTNAP2 encoding contactin-associated protein 2 (CASPR2), which harbours mutations associated to autism, schizophrenia, and intellectual disability. Antibodies targeting CASPR2 have also been recently described in patients with several neurological disorders, such as neuromyotonia, Morvan's syndrome, and limbic encephalitis. Despite the clear implication of CNTNAP2 and CASPR2 in neuropsychiatric disorders, the pathogenic mechanisms associated with alterations in CASPR2 function are unknown. Here, we show that Caspr2 is expressed in excitatory synapses in the cortex, and that silencing its expression in vitro or in vivo decreases the synaptic expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and the amplitude of AMPA receptor-mediated currents. Furthermore, Caspr2 loss of function blocks synaptic scaling in vitro and experience-dependent homoeostatic synaptic plasticity in the visual cortex. Patient CASPR2 antibodies decrease the dendritic levels of Caspr2 and synaptic AMPA receptor trafficking, and perturb excitatory transmission in the visual cortex. These results suggest that mutations in CNTNAP2 may contribute to alterations in AMPA receptor function and homoeostatic plasticity, and indicate that antibodies from anti-CASPR2 encephalitis patients affect cortical excitatory transmission.

Memory of recent oxygen experience switches pheromone valence in Caenorhabditis elegans.

Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2 This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons. RMG is gap-junctionally coupled to the ASK and ADL pheromone sensors that respectively drive pheromone attraction and repulsion. Prior O2 experience has opposite effects on the pheromone responsiveness of these neurons. These circuit changes provide a physiological correlate of altered pheromone valence. Our results suggest C. elegans stores a memory of recent O2 experience in the RMG circuit and illustrate how a circuit is flexibly sculpted to guide behavioral decisions in a context-dependent manner.

Plasticity in auditory categorization is supported by differential engagement of the auditory-linguistic network.

To construct our perceptual world, the brain categorizes variable sensory cues into behaviorally-relevant groupings. Categorical representations are apparent within a distributed fronto-temporo-parietal brain network but how this neural circuitry is shaped by experience remains undefined. Here, we asked whether speech and music categories might be formed within different auditory-linguistic brain regions depending on listeners' auditory expertise. We recorded EEG in highly skilled (musicians) vs. less experienced (nonmusicians) perceivers as they rapidly categorized speech and musical sounds. Musicians showed perceptual enhancements across domains, yet source EEG data revealed a double dissociation in the neurobiological mechanisms supporting categorization between groups. Whereas musicians coded categories in primary auditory cortex (PAC), nonmusicians recruited non-auditory regions (e.g., inferior frontal gyrus, IFG) to generate category-level information. Functional connectivity confirmed nonmusicians' increased left IFG involvement reflects stronger routing of signal from PAC directed to IFG, presumably because sensory coding is insufficient to construct categories in less experienced listeners. Our findings establish auditory experience modulates specific engagement and inter-regional communication in the auditory-linguistic network supporting categorical perception. Whereas early canonical PAC representations are sufficient to generate categories in highly trained ears, less experienced perceivers broadcast information downstream to higher-order linguistic brain areas (IFG) to construct abstract sound labels.

Fluoxetine-induced plasticity in the visual cortex outlasts the duration of the naturally occurring critical period.

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments, such as the antidepressant fluoxetine, can reactivate a critical period-like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine-induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period and continued as long as fluoxetine was administered. However, this fluoxetine-induced plasticity period ended as soon as the drug was not given. These features of antidepressant-induced plasticity may be useful when designing treatment strategies involving long-term antidepressant treatment in humans.

Differential modulation of courtship behavior and subsequent aggression by octopamine, dopamine and serotonin in male crickets.

Aggression is a behavioral strategy for securing limited resources and its expression is strongly influenced by their presence and value. In particular, males are generally thought to guard females after mating to ward off other males, but the underlying control mechanisms are unknown. Here, we investigated the role of amines on male courtship behavior and its subsequent effect on male-male aggression in crickets (Gryllus bimaculatus). Contrary to the guarding hypothesis, female presence alone had no immediate effect on male-male aggression. Furthermore, confirming studies on other species, prior female contact, but not necessarily courtship or copulation, promoted subsequent male-male aggression in subordinate, but not socially naive crickets. This promoting effect of female contact is transient and slowly wanes after her removal. Selective aminergic receptor antagonists revealed that the promoting effect of prior female contact on male-male aggression is mediated by octopamine (OA), as well as by serotonin (5HT) acting most likely via 5HT1 and/or 5HT7 like receptors. This contrasts the role of 5HT2-like receptors in maintaining reduced aggressiveness after social defeat. Furthermore, while dopamine (DA) is necessary for the recovery of aggression in subordinates after defeat, it appears to play no part in female induced aggression. Male courtship, on the other hand, is selectively promoted by DA and 5HT, again most likely via 5HT1 and/or 5HT7 like receptors, but not by OA. We conclude that OA, DA and 5HT each differentially modulate different aspects of courtship and aggressive behavior in a context specific fashion.

Consequences of multilingualism for neural architecture.

Language has the power to shape cognition, behavior, and even the form and function of the brain. Technological and scientific developments have recently yielded an increasingly diverse set of tools with which to study the way language changes neural structures and processes. Here, we review research investigating the consequences of multilingualism as revealed by brain imaging. A key feature of multilingual cognition is that two or more languages can become activated at the same time, requiring mechanisms to control interference. Consequently, extensive experience managing multiple languages can influence cognitive processes as well as their neural correlates. We begin with a brief discussion of how bilinguals activate language, and of the brain regions implicated in resolving language conflict. We then review evidence for the pervasive impact of bilingual experience on the function and structure of neural networks that support linguistic and non-linguistic cognitive control, speech processing and production, and language learning. We conclude that even seemingly distinct effects of language on cognitive operations likely arise from interdependent functions, and that future work directly exploring the interactions between multiple levels of processing could offer a more comprehensive view of how language molds the mind.

Physiological role for amyloid precursor protein in adult experience-dependent plasticity.

Changes in neural circuits after experience-dependent plasticity are brought about by the formation of new circuits via axonal growth and pruning. Here, using a combination of electrophysiology, adeno-associated virus-delivered fluorescent proteins, analysis of mutant mice, and two-photon microscopy, we follow long-range horizontally projecting axons in primary somatosensory cortex before and after selective whisker plucking. Whisker plucking induces axonal growth and pruning of horizontal projecting axons from neurons located in the surrounding intact whisker representations. We report that amyloid precursor protein is crucial for axonal pruning and contributes in a cell autonomous way.

Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male-Male Social Interaction.

Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male-male social experience. Following the resident-intruder paradigm, Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IH currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc-expressing interneurons.SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male-male social chemosensory encounters. We show that the plasticity-associated immediate-early gene Arc is selectively expressed in IGCs from resident males following the resident-intruder assay. After behavior, Arc-expressing IGCs are more strongly excited by sensory input stimulation and MC activation is suppressed. Arc-expressing IGCs do not show increased excitatory synaptic drive but instead show increased intrinsic excitability. These data indicate that MC-IGC plasticity is induced after male-male social chemosensory encounters, resulting in enhanced MC suppression by Arc-expressing IGCs.

Direct intertectal inputs are an integral component of the bilateral sensorimotor circuit for behavior in Xenopus tadpoles.

The circuit controlling visually guided behavior in nonmammalian vertebrates, such as Xenopus tadpoles, includes retinal projections to the contralateral optic tectum, where visual information is processed, and tectal motor outputs projecting ipsilaterally to hindbrain and spinal cord. Tadpoles have an intertectal commissure whose function is unknown, but it might transfer information between the tectal lobes. Differences in visual experience between the two eyes have profound effects on the development and function of visual circuits in animals with binocular vision, but the effects on animals with fully crossed retinal projections are not clear. We tested the effect of monocular visual experience on the visuomotor circuit in Xenopus tadpoles. We show that cutting the intertectal commissure or providing visual experience to one eye (monocular visual experience) is sufficient to disrupt tectally mediated visual avoidance behavior. Monocular visual experience induces asymmetry in tectal circuit activity across the midline. Repeated exposure to monocular visual experience drives maturation of the stimulated retinotectal synapses, seen as increased AMPA-to-NMDA ratios, induces synaptic plasticity in intertectal synaptic connections, and induces bilaterally asymmetric changes in the tectal excitation-to-inhibition ratio (E/I). We show that unilateral expression of peptides that interfere with AMPA or GABAA receptor trafficking alters E/I in the transfected tectum and is sufficient to degrade visuomotor behavior. Our study demonstrates that monocular visual experience in animals with fully crossed visual systems produces asymmetric circuit function across the midline and degrades visuomotor behavior. The data further suggest that intertectal inputs are an integral component of a bilateral visuomotor circuit critical for behavior. NEW & NOTEWORTHY The developing optic tectum of Xenopus tadpoles represents a unique circuit in which laterally positioned eyes provide sensory input to a circuit that is transiently monocular, but which will be binocular in the animal's adulthood. We challenge the idea that the two lobes of tadpole optic tectum function independently by testing the requirement of interhemispheric communication and demonstrate that unbalanced sensory input can induce structural and functional plasticity in the tectum sufficient to disrupt function.