Biology subjects

Remage-Healey, L.

Publications and source records attributed to Remage-Healey, L..

7 recordsLinked to original sources

bioRxiv2026

Similar Synaptic and Current Input Properties of Aromatase and Nonaromatase Neurons in the Zebra Finch Auditory Telencephalon

Abstract/SummaryEstrogens, commonly known for their role in sexual development and maturation, support a wide variety of brain functions, including cognition, neuroprotection, and sensory processing. For example, in a songbird auditory forebrain region, caudomedial nidopallium (NCM), neuroestrogens are elevated in response to conspecific vocal and social stimuli; in turn, elevated neuroestrogens in NCM are known to rapidly enhance auditory processing independent of sex. Despite the pivotal role of neuroestrogens for brain function, it remains largely unknown whether aromatase (neuroestrogen-synthesizing) neurons differ in their cellular and physiological properties from non-aromatase-expressing neurons, as might be expected from specializations seen in other steroidogenic cell types (e.g., adrenal cells). Therefore, we systematically profiled aromatase and nonaromatase expressing NCM neurons to determine how they might differ in synaptic and current input properties, using ex vivo whole-cell electrophysiology followed by immunohistochemistry to reveal aromatase expression. Current-clamp recordings revealed no differences between aromatase and nonaromatase neurons, aside from a modest divergence in the time to reach peak membrane afterhyperpolarization. Similarly, voltage-clamp recordings of post-synaptic currents revealed no significant differences between the two cell types, suggesting that they share similar synaptic input density. Therefore, aromatase and nonaromatase NCM neurons share similar intrinsic membrane properties (e.g. excitability) and synaptic input dynamics in the higher songbird pallium. Our findings leave open the possibility that diverging computational and/or modulatory roles for aromatase vs. non-aromatase neurons could be due to projection- or neurochemical-specificity in their afferents and efferents. Significance StatementNeuroestrogens, locally synthesized in the brain by aromatase-expressing neurons, modulate neural circuit function across diverse brain regions, yet it remains unclear whether these cells represent a specialized neuronal population. We used whole-cell electrophysiology and post hoc identification of recorded neurons in the zebra finch auditory forebrain to compare the intrinsic and synaptic properties of aromatase and nonaromatase neurons. Confirming and extending previous findings, we show that aromatase-expressing neurons are not defined by unique electrophysiological properties. Instead, they appear to be functionally integrated within auditory circuits, supporting an alternative idea that neuroestrogen signaling acts through flexible neuromodulatory mechanisms rather than specialized neuronal properties. These findings do not exclude the possibility that aromatase neurons receive selective modulatory input from other brain regions.

neuroscience↗

bioRxiv2026

Parental state dynamically reshapes auditory processing of offspring vocalizations in zebra finches

Parental care is critical for offspring survival. For many species, including humans, auditory cues unique to dependent offspring, such as baby cries, elicit the necessary behavior from parents to care for young. Despite this, we know little about how the brain encodes auditory cues specific to offspring. Zebra finches are an excellent model to study this. Zebra finches are biparental, meaning both male and female parents raise the young and rely on auditory cues (begging calls) to elicit chick feeding responses (parental behavior). Begging calls also become individually identifiable by the parents, necessitating higher-order learning/ association neural processes. It is well established that the caudomedial nidopallium (NCM), a higher-order region of secondary pallial cortex (analogous to the mammalian secondary auditory cortex), is involved in the perception of complex auditory signals in birds. It is unknown, however, if/how NCM responds to offspring begging calls. To begin testing this, we used high density silicon probes to record single-unit in vivo electrophysiology activity in the NCM of adult parenting and non-parenting zebra finches exposed to playbacks of their own chicks begging calls (parents only), novel age-matched begging calls (parents and non-parents), as well as novel adult male song and pure tone controls. Our results show that NCM neurons in parents respond more strongly (i.e., higher evoked firing rates) to both their own and novel chick begging calls and have higher baseline (spontaneous) firing rates in narrow spiking units relative to non-parents. Furthermore, NCM neurons in parenting females tend to show more selective responses towards their own chick begging calls, whereas those in males do not show similar levels of selectivity. These studies lay essential groundwork for future studies on how auditory responses can elicit parental behavior and how these responses may change over the chick-rearing period.

neuroscience↗

bioRxiv2026

Organization, Neuronal Composition, and Dynamics of Neuronal Ensembles in the Songbird Auditory Forebrain

Auditory learning is a key component of vocal learning and communication. Neurons involved in auditory learning are typically examined as single encoders, but there is increasing evidence that the coincident activity of groups of neurons, or ensembles, is important for the processing and transmission of sensory information. In songbirds, a forebrain region analogous to mammalian secondary auditory cortex, the caudomedial nidopallium (NCM), is crucial for representing and learning auditory signals. In the awake state, NCM neurons exhibit stimulus-specific adaptation in response to repeated presentation of song stimuli, considered a form of auditory working memory. Yet, how complex stimuli like song are encoded by networks of excitatory and inhibitory neurons is essentially unknown. Using in-vivo single-unit electrophysiology, we systematically unveiled neuronal ensembles that operate at high temporal precision (< 10 ms) across the NCM of awake zebra finches (Taeniopygia guttata). Our data show that multiple ensembles are concurrently activated by song with high temporal precision, and that their neuronal composition is heterogeneous, topographically proximate, and biased towards excitatory members. NCM ensembles adapt to song playback and, notably, become more stimulus selective over tens of minutes, accompanied by fast remodeling (membership gain and/or loss) during adaptation. Altogether, our results suggest that song representations in the forebrain can be conveyed by multiple, dynamic network ensembles in parallel. These findings advance our knowledge of the composition, dynamics, and neuronal network reorganization of ensembles as complex sensory stimuli become increasingly familiar.

neuroscience↗

bioRxiv2023

Top-down, auditory pallial regulation of the social behavior network

Social encounters rely on sensory cues that carry nuanced information to guide social decision-making. While high-level features of social signals are processed in the telencephalic pallium, nuclei controlling social behaviors, called the social behavior network (SBN), reside mainly in the diencephalon. Although it is well known how mammalian olfactory pallium interfaces with the SBN, there is little information for how pallial processing of other sensory modalities can modulate SBN circuits. This is surprising given the importance of complex vocalizations, for example, for social behavior in many vertebrate taxa such as humans and birds. Using gregarious and highly vocal songbirds, female Zebra finches, we asked to what extent auditory pallial circuits provide consequential input to the SBN as it processes social sensory cues. We transiently inactivated auditory pallium of female Zebra finches during song playback and examined song-induced activation in SBN nuclei. Auditory pallial inactivation impaired responses to song specifically within the lateral ventromedial nucleus of the hypothalamus (VMHl), providing the first evidence in vertebrates of a connection between auditory pallium and the SBN. This same treatment elevated feeding behavior, which also correlated with VMHl activation. This suggests that signals from auditory pallium to VMHl can tune the balance between social attention and feeding drive. A descending influence of sensory pallium on hypothalamic circuits could therefore provide a functional connection for the integration of social stimuli with internal state to influence social decision-making. SignificanceSensory cues such as vocalizations contain important social information. These social signals can be substantially nuanced, containing information about vocalizer identity, prior experience, valence, and emotional state. Processing these features of vocalizations necessitates processing the fast, complex sound streams in song or speech, which depends on circuits in pallial cortex. But whether and how this information is then transferred to social circuits in limbic and hypothalamic regions remains a mystery. Here, we identify a top-down influence of the songbird auditory pallium on one specific node of the social behavior network within the hypothalamus. Descending functional connections such as these may be critical for the wide range of vertebrate species that rely on intricate sensory communication signals to guide social decision-making.

neuroscience↗

bioRxiv2020

Genetically-identified cell types in avian pallium mirror core principles of excitatory and inhibitory neurons in mammalian cortex

In vertebrates, advanced cognitive abilities are associated with a highly developed telencephalic pallium. In mammals, the six-layered neocortex of the pallium is composed of excitatory neurons and inhibitory interneurons, organized across layers into microcircuits. These organizational principles are proposed to support efficient, high-level information processing. Comparative perspectives across vertebrates provide a lens to understand what common features of pallium are important for complex cognition. For non-mammalian vertebrates that exhibit complex cognitive abilities, such as birds, the physiology of identified pallial cell types and their circuit organization are largely unresolved. Using viral tools to target excitatory vs. inhibitory neurons in the zebra finch auditory association pallium, we systematically tested predictions derived from mammalian neocortex. We identify two segregated neuronal populations that exhibit profound physiological and computational similarities with mammalian excitatory and inhibitory neocortical cells. Specifically, despite dissimilarities in gross architecture, avian association pallium exhibits neocortex-typical coding principles, and inhibitory-dependent cortical synchrony, gamma oscillations, and local suppression. Our findings suggest parallel evolution of physiological and network roles for pallial cell types in amniotes with substantially divergent pallial organization.

neuroscience↗

bioRxiv2020

Dopamine D1 receptor activation drives plasticity in the songbird auditory pallium

Vocal learning species must form and extensively hone associations between sounds and social contingencies. In songbirds, dopamine signaling guides song motor-production, variability, and motivation, but it is unclear how dopamine regulates fundamental auditory associations for learning new sounds. We hypothesized that dopamine regulates learning in the auditory pallium, in part by interacting with local neuroestradiol signaling. Here, we show that zebra finch auditory neurons frequently coexpress D1 receptor (D1R) protein, neuroestradiol-synthase, GABA, and parvalbumin. Auditory classical conditioning increased neuroplasticity gene induction in D1R-positive neurons. In vitro, D1R pharmacological activation reduced the amplitude of GABAergic and glutamatergic currents, and increased the latters frequency. In vivo, D1R activation reduced the firing of putative interneurons, increased the firing of putative excitatory neurons, and made both neuronal types unable to adapt to novel stimuli. Together, these data support the hypothesis that dopamine acting via D1Rs modulates learning and memory in the songbird sensory cortex.

neuroscience↗

bioRxiv2019

Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbird

Birdsong, like human speech, is learned early in life by first memorizing an auditory model. Once memorized, birds compare their own burgeoning vocalizations to their auditory memory, and adjust their song to match the model. While much is known about this latter part of vocal learning, less is known about how initial auditory experiences are formed and consolidated. In both adults and developing songbirds, there is strong evidence suggesting the caudomedial nidopallium (NCM), a higher order auditory forebrain area, is the site of auditory memory consolidation. However, the mechanisms that facilitate this consolidation are poorly understood. One likely mechanism is 17{beta}-estradiol (E2), which is associated with speech-language development and disorders in humans, and is abundant in both mammalian temporal cortex and songbird NCM. Circulating E2 is also elevated during the auditory memory phase, and in NCM immediately after song learning sessions, suggesting it functions to encode recent auditory experience. Therefore, we tested a role for E2 production in auditory memory consolidation during development using a comprehensive set of investigations to ask this question at the level of neuroanatomy, neurophysiology, and behavior. Our results demonstrate that while systemic estrogen synthesis blockade regulates juvenile song production, inhibiting E2 synthesis locally within NCM does not adversely affect song learning outcomes. Surprisingly, early life E2 manipulations in NCM modify the neural representations of birds own song and the model tutor song in both NCM and a downstream sensorimotor nucleus (HVC). Further, we show that the capacity to synthesize neuroestrogens remains high throughout development alongside substantial changes in NCM cell density across age. Taken together, these findings suggest that E2 plays a multifaceted role during development, and demonstrate that contrary to prediction, unilateral post-training estrogen synthesis blockade in the auditory cortex does not negatively impact vocal learning. Acute downregulation of neuroestrogens are therefore likely permissive for juvenile auditory memorization, while neuroestrogen synthesis influences communication production and representation in adulthood.

neuroscience↗