Postsynaptic neural activity regulates neuronal addition in the adult avian song control system

Abstract

A striking feature of the nervous system is that it shows extensive plasticity of structure and function that allows animals to adjust to changes in their environment. Neural activity plays a key role in mediating experience-dependent neural plasticity and, thus, creates a link between the external environment, the nervous system, and behavior. One dramatic example of neural plasticity is ongoing neurogenesis in the adult brain. The role of neural activity in modulating neuronal addition, however, has not been well studied at the level of neural circuits. The avian song control system allows us to investigate how activity influences neuronal addition to a neural circuit that regulates song, a learned sensorimotor social behavior. In adult white-crowned sparrows, new neurons are added continually to the song nucleus HVC (proper name) and project their axons to its target nucleus, the robust nucleus of the arcopallium (RA). We report here that electrical activity in RA regulates neuronal addition to HVC. Decreasing neural activity in RA by intracerebral infusion of the GABA A receptor agonist muscimol decreased the number of new HVC neurons by 56%. Our results suggest that postsynaptic electrical activity influences the addition of new neurons into a functional neural circuit in adult birds. Songbirds provide a tractable model for understanding the mechanisms that regulate new neuron addition into functional circuits. Song is a learned sensorimotor behavior that is important for songbird reproduction. Song learning and production are regulated by a discrete, well-characterized neural circuit that includes HVC (proper name) and its target nucleus, the robust nucleus of the arcopallium (RA), both located in the avian forebrain (Fig. 1A) (2). In the adult Gambel's white-crowned sparrow (WCS), the song control system shows extreme seasonal neuroplasticity (reviewed in ref.3). Early in the breeding season, HVC and RA of WCS nearly double in volume. The increase in HVC volume results largely from an increase in new neuron incorporation, whereas the increase in RA volume results from increases in neuron size and spacing, but not number. RA neurons also show increased spontaneous electrical activity in the breeding season (4, 5). WCS typically produce only one song type that is longer and more stereotyped in structure during the breeding season (6, 7).HVC contains three types of neurons: HVC→RA and HVC→area X projection neurons and interneurons. During seasonal growth, most, if not all, neurons incorporated into HVC project to RA (ref. 8, but see ref. 9). Neural progenitor cells are born at the dorsal and ventral portion of the lateral ventricle and migrate from the ventricular zone (VZ) to HVC within 1 wk after birth (10). Over the next 2-3 wk, new neurons send axonal projections to RA (11). These new HVC→RA projection neurons are functional; they can fire action potentials in response to sound stimuli (12).Environment and experience play important roles in both brain development and adult neurogenesis. For example, duri...

Dissociable Effects on Birdsong of Androgen Signaling in Cortex-Like Brain Regions of Canaries

“…These results suggest that variation in syllable-type usage is encoded in HVC, but retrograde feedback from RA can affect this process due to its regulation of the addition of new neurons into HVC (Larson et al, 2013).…”

“…Therefore, in addition to the potential actions of estrogens of a gonadal origin acting in the POM and HVC to regulate song, actions of estrogens generated from testosterone within these nuclei is also possible. There is also evidence that neural activity/hormone action in one region can influence morphological or neurophysiology characteristics in downstream or upstream brain regions (Brenowitz and Lent, 2002;Meitzen et al, 2007;Larson et al, 2013;Brenowitz, 2015;Alward et al, 2016c), which could affect control of song. All song features listed in italics are predicted to be controlled by androgens and/or estrogens based on the results of past studies (Spiro et al, 1999;Long and Fee, 2008;Picardo et al, 2016).…”

“…As mentioned above, for HVC, the goal was to place the cannula tips adjacent (lateral) to the nucleus to minimize damage to the nucleus (Meitzen et al, 2007). For RA, the goal was to place cannula tips directly above or adjacent to the nucleus for the same reason (Meitzen et al, 2007;Larson et al, 2013). For HVC, only distance of the cannula tip lateral to HVC was used to determine specificity because most cannula tips did not occur ventral to HVC, making a meaningful analysis of variation based on dorsoventral distance to HVC and whole-song stereotypy impossible.…”

Neurogenesis in the Adult Avian Song-Control System

“…Inhibiting activity in breeding-condition birds by infusing RA with the GABA A receptor agonist muscimol decreased the number of new neurons in HVC of adult white-crowned sparrows by 56% (Fig. 4) (Larson et al 2013). Increasing RA activity in nonbreeding condition birds by infusing KCl increased the number of new HVC neurons by 95% (Fig.…”

“…New neurons added to the olfactory bulb in mammals, in contrast, are interneurons (Lledo et al 2006;De Marchis et al 2007), and those added to the DG are granule cells that synapse locally on the hippocampal hilus and CA3 (Toni et al 2008). HVC, therefore, provides a unique model for investigating the incorporation of new neurons into long-range neural circuits, and facilitates manipulations of target cells to examine postsynaptic influences on the addition of new afferent neurons (e.g., Larson et al 2013). …”