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. 2015 Jan 22:284:522-535.
doi: 10.1016/j.neuroscience.2014.10.023. Epub 2014 Oct 19.

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus

B A Pawlisch  1 , L Remage-Healey  2
Affiliations

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus

B A Pawlisch et al. Neuroscience. .

Abstract

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity.

Keywords: HVC; aromatase; estrogen; nidopallium; nucleus interfacialis; songbird.

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Figures

Figure 1
Figure 1
A. Schematic of a sagittal view of the auditory and vocal motor pathways of the male zebra finch brain, showing the placements of a retrodialysis probe and electrodes during retrodialysis and dual electrophysiological recording. The green triangle depicts the presence of a retrodialysis probe within the caudomedial nidopallium (NCM), which is a higher order auditory region that contains aromatase-positive neurons. The blue triangle represents the presence of an extracellular electrode into the nucleus interfacialis of the nidopallium (NIf), a region connecting auditory and vocal motor regions, and the red triangle represents the presence of an extracellular electrode in HVC (proper name), a vocal motor region critical for singing behavior in male songbirds. Other abbreviations: the nucleus ovoidalis (Ov), Field L complex (Field L), caudal mesopallium (CM), and robust nucleus of the arcopallium (RA). B. Exemplar of simultaneous electrophysiological activity in NIf and HVC. Supra-threshold activity is shown in raster form above the multi-unit electrophysiological activity in HVC and NIf. Supra-threshold activity was used to measure firing rate, Z score, and d' REV (for more detail see the methods). Song, as shown as a waveform, elicits auditory-evoked activity above baseline activity simultaneously in NIf and HVC.
Figure 2
Figure 2
Schematic of the location of lesions from electrodes in NIf and immediately surrounding NIf. NIf is found ventral to the mesopallial lamina (LaM) and just dorsal to the pallial-subpallial lamina (PSL). The Field L complex (Field L) extends caudo-dorsally along the PSL. NIf is shaded and contains placement lesions showing that many of the lesions are inside of NIf (n=11), and some were present outside of the NIf (n=7). Two were not depicted that were too lateral to be in NIf and thus were outside of the plain of section of the diagram. Some lesions are not depicted due to tissue degradation/loss.
Figure 3
Figure 3
Multi-unit electrophysiological activity in NIf. A. Photomicrograph of the lesion inside NIf (black arrow points to lesion). B. Exemplar of raw cross-correlograms highlighting the relationship between NIf and HVC activity. The time of the peak denotes the difference in timing between NIf and HVC activity; the size of the peak denotes the strength of the correlation in activity between NIf and HVC. The large peak before zero shows that activity in NIf occurs slightly before activity in HVC. C. Mean (+ SEM) spike rate during auditory stimuli before (pre), during (E2), and after (post) estradiol treatment. For each treatment, the same stimuli were presented: a male zebra finch's own song or bird's own song (BOS), that bird's own song reversed (REV), another male zebra finch's song (CON), and white noise (WN) in a randomized order (see methods for more details). The asterisks denote significant post-hoc tests of the main effect of song stimuli between BOS, CON, REV, and WN.
Figure 4
Figure 4
Single-unit electrophysiological activity in NIf. A. Mean (+ SEM) spike rate during auditory stimuli before, during, and after estradiol treatment. The asterisk denotes significant post-hoc tests of the main effect of treatment between pre, E2, and post. B. Mean (+ SEM) Z score during auditory stimuli before, during, and after estradiol treatment. The same statistical tests show similar results for Z score. The asterisk denotes significant post-hoc test of the main effect of treatment between pre, E2, and post. C. Mean (+ SEM) baseline firing rate of NIf neurons before, during, and after estradiol treatment. As in the evoked responses in A–B, the same statistical tests show similar result for baseline firing rate. The asterisk denotes significant post-hoc tests of the main effect of treatment between pre, E2, and post. D. Top, Principle component analysis plot of multi-unit electrophysiological recording, showing three auditory units in NIf. Below, Overlay of the 50 random spike waveforms from the same single units.
Figure 5
Figure 5
Electrophysiological activity in NIF-surround. A. Photomicrograph of the lesion outside of NIf (black arrow points to lesion). B. Exemplar of raw cross-correlograms highlighting in the relationship between NIf-surround and HVC activity showing no clear `leading' relationship between the activity of neurons in the immediate surround of NIf and the activity of HVC neurons. C. Multi-unit electrophysiological activity in NIf-surround. Mean (+ SEM) firing rate during auditory stimuli before, during, and after estradiol treatment. D. Mean (+ SEM) baseline firing rate during auditory stimuli before, during, and after estradiol treatment. The asterisk denotes significant post-hoc tests of the main effect of treatment between pre, E2, and post. E. Top, Principle component analysis plot of multi-unit electrophysiological recording, showing two auditory units in HVC. Below, Overlay of the 50 random spike waveforms from the same single units.
Figure 6
Figure 6
Electrophysiological activity in HVC. A. Multi-unit electrophysiological activity in HVC. Mean (+ SEM) firing rate during auditory stimuli before, during, and after estradiol treatment. The asterisk denotes significant post-hoc tests of the main effect of song stimuli between BOS, CON, REV, and WN. B. Single-unit electrophysiological activity in HVC. After single-unit sorting, the same statistical tests show similar results for firing rate during auditory stimuli. C. Single-unit electrophysiological activity in HVC. Mean (+ SEM) d' REV during auditory stimuli before, during, and after estradiol treatment. Inset shows individual data for all single units for d'REV for the BOS stimulus.
Figure 7
Figure 7
Single-unit electrophysiological activity in NIf shows that selectivity for the BOS is reduced during fadrozole treatment in NCM. A. Mean (+ SEM) Z score during auditory stimuli before, during, and after fadrozole treatment. B. Mean (+ SEM) d' REV during auditory stimuli before, during, and after fadrozole treatment. The asterisk denotes significant post-hoc test of the main effect of treatment between pre, FAD, and post.
Figure 8
Figure 8
Single-unit electrophysiological activity in HVC shows that selectivity for the BOS is reduced during fadrozole treatment in NCM. A. Mean (+ SEM) Z score during auditory stimuli before, during, and after fadrozole treatment. The asterisk denotes significant post-hoc tests of the interaction of treatment and song stimulus. B. Mean (+ SEM) d' REV during auditory stimuli before, during, and after fadrozole treatment.
Figure 9
Figure 9
Concurrent electrophysiological activity in NIf and HVC shows a direct influence of fadrozole in NCM on the correlated activity between NIf and HVC. A. Prior to fadrozole treatment, a trend line shows there is a significant correlation between NIf and HVC. B. During fadrozole treatment, there is no longer a significant correlation between NIf and HVC activity. C. After fadrozole treatment, there is also no longer a significant correlation between NIf and HVC activity.
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