Melissa J. Coleman

Brain estrogens rapidly strengthen auditory encoding and guide song preference in a songbird

Higher cognitive function depends on accurate detection and processing of subtle features of sensory stimuli. Such precise computations require neural circuits to be modulated over rapid timescales, yet this modulation is poorly understood. Brain-derived steroids (neurosteroids) can act as fast signaling molecules in the vertebrate central nervous system and could therefore modulate sensory processing and guide behavior, but there is no empirical evidence for this possibility. Here we report that acute inhibition of estrogen production within a cortical-like region involved in complex auditory processing disrupts a songbird’s ability to behaviorally respond to song stimuli. Identical manipulation of local estrogen levels rapidly changes burst firing of single auditory neurons. This acute estrogen-mediated modulation targets song and not other auditory stimuli, possibly enabling discrimination among species-specific signals. Our results demonstrate a crucial role for neuroestrogen synthesis among vertebrates for enhanced sensory encoding. Cognitive impairments associated with estrogen depletion, including verbal memory loss in humans, may therefore stem from compromised moment-by-moment estrogen actions in higher-order cortical circuits.

A synaptic basis for auditory-vocal integration in the songbird

Songbirds learn to sing by memorizing a tutor song that they then vocally mimic using auditory feedback. This developmental sequence suggests that brain areas that encode auditory memories communicate with brain areas for learned vocal control. In the songbird, the secondary auditory telencephalic region caudal mesopallium (CM) contains neurons that encode aspects of auditory experience. We investigated whether CM is an important source of auditory input to two sensorimotor structures implicated in singing, the telencephalic song nucleus interface (NIf) and HVC. We used reversible inactivation methods to show that activity in CM is necessary for much of the auditory-evoked activity that can be detected in NIf and HVC of anesthetized adult male zebra finches. Furthermore, extracellular and intracellular recordings along with spike-triggered averaging methods indicate that auditory selectivity for the birds own song is enhanced between CM and NIf. We used lentiviral-mediated tracing methods to confirm that CM neurons directly innervate NIf. To our surprise, these tracing studies also revealed a direct projection from CM to HVC. We combined irreversible lesions of NIf with reversible inactivation of CM to establish that CM supplies a direct source of auditory drive to HVC. Finally, using chronic recording methods, we found that CM neurons are active in response to song playback and during singing, indicating their potential importance to song perception and processing of auditory feedback. These results establish the functional synaptic linkage between sites of auditory and vocal learning and may identify an important substrate for learned vocal communication.

Synaptic Transformations Underlying Highly Selective Auditory Representations of Learned Birdsong

Stimulus-specific neuronal responses are a striking characteristic of several sensory systems, although the synaptic mechanisms underlying their generation are not well understood. The songbird nucleus HVC (used here as a proper name) contains projection neurons (PNs) that fire temporally sparse bursts of action potentials to playback of the birds own song (BOS) but are essentially silent when presented with other acoustical stimuli. To understand how such remarkable stimulus specificity emerges, it is necessary to compare the auditory-evoked responsiveness of the afferents of HVC with synaptic responses in identified HVC neurons. We found that inactivating the interfacial nucleus of the nidopallium (NIf) could eliminate all auditory-evoked subthreshold activity in both HVC PN types, consistent with NIf serving as the major auditory afferent of HVC. Simultaneous multiunit extracellular recordings in NIf and intracellular recordings in HVC revealed that NIf population activity and HVC subthreshold responses were similar in their selectivity for BOS and that NIf spikes preceded depolarizations in all HVC cell types. These results indicate that information about the BOS as well as other auditory stimuli is transmitted synaptically from NIf to HVC. Unlike HVC PNs, however, HVC-projecting NIf neurons fire throughout playback of BOS as well as non-BOS stimuli. Therefore, temporally sparse BOS-evoked firing and enhanced BOS selectivity, manifested as an absence of suprathreshold responsiveness to non-BOS stimuli, emerge in HVC. The transformation to a sparse auditory representation parallels differences in NIf and HVC activity patterns seen during singing, which may point to a common mechanism for encoding sensory and motor representations of song.

Thalamic Gating of Auditory Responses in Telencephalic Song Control Nuclei

In songbirds, nucleus Uvaeformis (Uva) is the sole thalamic input to the telencephalic nucleus HVC (used as a proper name), a sensorimotor structure essential to learned song production that also exhibits state-dependent responses to auditory presentation of the birds own song (BOS). The role of Uva in influencing HVC auditory activity is unknown. Using in vivo extracellular and intracellular recordings in urethane-anesthetized zebra finches, we characterized the auditory properties of Uva and examined its influence on auditory activity in HVC and in the telencephalic nucleus interface (NIf), the main auditory afferent of HVC and a corecipient of Uva input. We found robust auditory activity in Uva and determined that Uva is innervated by the ventral nucleus of lateral lemniscus, an auditory brainstem component. Thus, Uva provides a direct linkage between the auditory brainstem and HVC. Although low-frequency electrical stimulation in Uva elicited short-latency depolarizing postsynaptic potentials in HVC neurons, reversibly silencing Uva exerted little effect on BOS-evoked activity in HVC neurons. However, high-frequency stimulation in Uva suppressed auditory-evoked synaptic and suprathreshold activity in all HVC neuron types, a process accompanied by decreased input resistance of individual HVC neurons. Furthermore, high-frequency stimulation in Uva simultaneously suppressed auditory activity in HVC and NIf. These results suggest that Uva can gate auditory responses in HVC through a mechanism that involves inhibition local to HVC as well as withdrawal of auditory-evoked excitatory drive from NIf. Thus, Uva could play an important role in state-dependent gating of auditory activity in telencephalic sensorimotor structures important to learned vocal control.

Neural mechanisms for the coordination of duet singing in wrens.

The brains of duetting wrens encode the entire song and not just the contribution of the individual. Plain-tailed wrens (Pheugopedius euophrys) cooperate to produce a duet song in which males and females rapidly alternate singing syllables. We examined how sensory information from each wren is used to coordinate singing between individuals for the production of this cooperative behavior. Previous findings in nonduetting songbird species suggest that premotor circuits should encode each bird’s own contribution to the duet. In contrast, we find that both male and female wrens encode the combined cooperative output of the pair of birds. Further, behavior and neurophysiology show that both sexes coordinate the timing of their singing based on feedback from the partner and suggest that females may lead the duet.

Characterization of Synaptically Connected Nuclei in a Potential Sensorimotor Feedback Pathway in the Zebra Finch Song System

Birdsong is a learned behavior that is controlled by a group of identified nuclei, known collectively as the song system. The cortical nucleus HVC (used as a proper name) is a focal point of many investigations as it is necessary for song production, song learning, and receives selective auditory information. HVC receives input from several sources including the cortical area MMAN (medial magnocellular nucleus of the nidopallium). The MMAN to HVC connection is particularly interesting as it provides potential sensorimotor feedback to HVC. To begin to understand the role of this connection, we investigated the physiological relation between MMAN and HVC activity with simultaneous multiunit extracellular recordings from these two nuclei in urethane anesthetized zebra finches. As previously reported, we found similar timing in spontaneous bursts of activity in MMAN and HVC. Like HVC, MMAN responds to auditory playback of the birds own song (BOS), but had little response to reversed BOS or conspecific song. Stimulation of MMAN resulted in evoked activity in HVC, indicating functional excitation from MMAN to HVC. However, inactivation of MMAN resulted in no consistent change in auditory responses in HVC. Taken together, these results indicate that MMAN provides functional excitatory input to HVC but does not provide significant auditory input to HVC in anesthetized animals. We hypothesize that MMAN may play a role in motor reinforcement or coordination, or may provide modulatory input to the song system about the internal state of the animal as it receives input from the hypothalamus.

Bidirectional scaling of vocal variability by an avian cortico‐basal ganglia circuit

Behavioral variability is thought to be critical for trial and error learning, but where such motor exploration is generated in the central nervous system is unclear. The zebra finch songbird species offers a highly appropriate model in which to address this question. The male song is amenable to detailed measurements of variability, while the brain contains an identified cortico‐basal ganglia loop that underlies this behavior. We used pharmacogenetic interventions to separately interrogate cortical and basal ganglia nodes of zebra finch song control circuitry. We show that bidirectional manipulations of each node produce near mirror image changes in vocal control: Cortical activity promotes song variability, whereas basal ganglia activity promotes song stability. Furthermore, female conspecifics can detect these pharmacogenetically elicited changes in song quality. Our results indicate that cortex and striatopallidum can jointly and reciprocally affect behaviorally relevant levels of vocal variability, and point to endogenous mechanisms for its control.

Dataset for: Bi-directional Scaling of Vocal Variability by an Avian Cortico-Basal Ganglia Circuit

Behavioral variability is thought to be critical for trial and error learning, but where such motor exploration is generated in the central nervous system is unclear. The zebra finch songbird species offers a highly appropriate model in which to address this question. The male song is amenable to detailed measurements of variability, while the brain contains an identified cortico-basal ganglia loop that underlies this behavior. We used pharmacogenetic interventions to separately interrogate cortical and basal ganglia nodes of zebra finch song control circuitry. We show that bi-directional manipulations of each node produce near mirror image changes in vocal control: Cortical activity promotes song variability whereas basal ganglia activity promotes song stability. Furthermore, female conspecifics can evaluate these pharmacogenetically-elicited changes in song quality. Our results indicate that cortex and striatopallidum can jointly and reciprocally affect behaviorally relevant levels of vocal variability, and point to endogenous mechanisms for its control.