Premotor synaptic plasticity limited to the critical period for song learning

Abstract

Synaptic plasticity has been hypothesized to underlie learning and memory. Understanding of how such plasticity might produce motor learning is limited, in part because of the paucity of model systems with a tractable learned behavior under control of a discrete neural circuit. Songbirds possess both of these traits, thereby providing an excellent model for studying vertebrate motor learning. We report unique evidence of long-term depression (LTD) in the juvenile songbird premotor robust nucleus of the arcopallium (RA). LTD induction at RA recurrent collateral synapses requires NMDA receptors, postsynaptic depolarization, and postsynaptic calcium, and can be reversed by high-frequency stimulation. In adult birds, which have exited the critical period for sensorimotor learning and cannot modify their song, we were no longer able to induce LTD at RA collateral synapses. Furthermore, testosterone-induced premature maturation of song in juveniles abolishes LTD. LTD in nucleus RA therefore makes an excellent candidate mechanism to mediate song learning during development and is well-suited to provide insight into other forms of vertebrate motor learning.L ong-lasting changes in synaptic strength, such as long-term potentiation (LTP) and long-term depression (LTD), have emerged as leading cellular models for the modification of neural circuitry during learning (1). In particular, associative learning induces LTP in the hippocampus (2). Skill learning can increase extracellular field potentials and partially occlude LTP at cortico-cortical synapses in the motor cortex (3), suggesting a similar role for cortical synaptic plasticity in motor learning. However, whether cortical synaptic plasticity underlies motor learning remains unclear, partly because of the distributed nature of cortical motor control and because of the paucity of behavioral paradigms controlled by sufficiently discrete cortical regions.Songbirds provide a highly advantageous model for studying the neural substrate of motor learning. Juvenile birds learn their songs during a critical period by first listening to an adult male tutor (sensory phase) and then practicing, and listening to themselves (sensorimotor phase), until they produce a stereotyped copy of the tutor's vocalization (4) (Fig. 1A). Early vocalizations are highly variable; after thousands of repetitions, however, the song is modified to match the tutor's song and becomes highly stereotyped, or "crystallized" (5).A discrete set of brain nuclei mediates song learning and production (6) (Fig. 1B). This song system can be divided into two functional pathways: the direct motor pathway, which is necessary for song production, and the anterior forebrain pathway (AFP), a cortical-basal ganglia pathway necessary for song learning and some forms of adult song plasticity, but not for the production of learned song (7-11). The premotor robust nucleus of the arcopallium (RA) occupies a crucial position in the song system as the final telencephalic nucleus in the direct motor pathway and the only motor...

Naturalistic stimulation drives opposing heterosynaptic plasticity at two inputs to songbird cortex

“…Data collection and analysis were not performed blind to the conditions of the experiments. No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 21,51,52 . All t-tests reported and two-tailed.…”

Task-related “cortical” bursting depends critically on basal ganglia input and is linked to vocal plasticity

“…First, LMAN bursting may be especially effective at modulating activity in the song motor nucleus RA, driving fluctuations in song that could function as motor exploration (24-27, 36, 45-47). Second, given recent evidence that LMAN can adaptively bias song output (16,48,49), it is also possible that song-locked bursting contributes to song plasticity directly, by instructing specific changes in the synaptic connections between the premotor nucleus HVC and RA via spike-timing-dependent mechanisms (24,27,36,47,50,51). Third, burst firing might also increase the synchrony of activity across multiple neurons in LMAN, and thus enhance their effectiveness in influencing RA and subsequent song output.…”

Translating Birdsong: Songbirds as a Model for Basic and Applied Medical Research

“…One likely locus for this more slowly developing component of learning is at HVC-RA synapses within the motor pathway. These synapses influence the activity of RA neurons (Hahnloser et al 2002, Long & Fee 2008; see sidebar ‘Motor sequence generation’) and thereby shape the spectral structure of ongoing song (Leonardo & Fee 2005, Sober et al 2008), and they are a site where LMAN inputs to RA are well-poised to drive synaptic plasticity (Mooney 1992, Sizemore & Perkel 2011). LMAN could instruct adaptive changes in motor circuitry by persistently imposing patterns of RA activity that eventually become engrained by spike timing dependent plasticity mechanisms acting on HVC to RA synapses (Troyer & Doupe 2000b, Swinehart & Abbott, 2005).…”