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Neuroestrogen inhibition destabilizes neuronal ensembles in songbird auditory forebrain

 

Felipe Cini

Felipe A. Cini (Luke Remage-Healy's Lab)

 Department of Neuroscience and Behavior at University of Massachusetts, Amherst, U.S.A 

In my PhD project, I use in-vivo electrophysiological recordings to investigate how neuroestrogen modulates neuronal ensembles in the auditory pallium of zebra finches in response to playback of conspecific songs.

Neuroestrogens rapidly modulate brain activity and support performance in learning tasks. Inhibiting estrogen synthesis leads to changes in electrophysiological activity of single neurons. Furthermore, neuronal ensembles, groups of co-activated cells (within a brief 6 ms time window), enhance information processing compared to single neuron activity. However, the effects of hormonal modulation on ensembles is virtually unknown. Therefore, we hypothesize that inhibiting neuroestrogen synthesis will: 1) change neuronal auditory responses, and 2) modify ensemble stability in the songbird zebra finch (Taeniopygia guttata). The caudomedial nidopallium (NCM), an auditory forebrain region of songbirds, is rich in aromatase (estrogen synthase). Using silicon probes for in-vivo electrophysiological recordings, combined with microdialysis, we recorded neuronal activity in NCM while administering aCSF (control) or fadrozole (FAD - an aromatase inhibitor). Single units, based on spike waveform, were classified as putative inhibitory or excitatory. Additionally, we used a combination of principal and independent component analyses to identify coordinated neuronal ensembles (range 3-10 neurons per ensemble). Our results showed that exposure to FAD induced a reduction in song-evoked single unit firing rate. This difference was driven by a stronger reduction in inhibitory unit response in the FAD condition, with excitatory units experiencing a more modest reduction in firing rate. Moreover, we found that half of the ensembles in the FAD condition underwent dynamic changes with repeated auditory stimuli, while the majority of the ensembles in the aCSF condition (> 90 percent) remained stable. These results suggest that inhibiting neuroestrogen synthesis destabilizes the coordination of membership in neuronal ensembles, driven by changes in inhibitory cell activity. Understanding more about how neuroestrogens modulate neuronal circuitry for auditory processing and learning, could unveil new therapeutic targets for conditions involving hormonal dysregulation or cognitive impairments.