Two distinct modes of forebrain circuit dynamics underlie temporal patterning in the vocalizations of young songbirds

“A key “cortical” area for mature singing is HVC (used as a proper name) (Nottebohm et al., 1976; Simpson and Vicario, 1990; Yu and Margoliash, 1996; Hahnloser et al., 2002).”

“At an early learning stage, they produce subsong: highly variable vocalizations similar to human babbling (Marler, 1970; Oller et al., 1976; Doupe and Kuhl, 1999).”

“A key “cortical” area for mature singing is HVC (used as a proper name) (Nottebohm et al., 1976; Simpson and Vicario, 1990; Yu and Margoliash, 1996; Hahnloser et al., 2002).”

“, 2005) which, like HVC, also projects to RA (Bottjer et al., 1984).”

“Vocalizations were recorded with custom-written Matlab software or with Sound Analysis Pro (Tchernichovski et al., 2000), which was configured to ensure that recordings were triggered on all quiet vocalizations of young birds (Aronov et al.”

“The goodness-of-fit of the exponential was estimated using the Lilliefors statistic (Lilliefors, 1969), a procedure similar to the Kolmogorov–Smirnov test but suitable for evaluating fits.”

“A key “cortical” area for mature singing is HVC (used as a proper name) (Nottebohm et al., 1976; Simpson and Vicario, 1990; Yu and Margoliash, 1996; Hahnloser et al., 2002).”

“An alternative hypothesis is that the timing of these early stereotyped song features is controlled elsewhere in the song system, perhaps by brain areas upstream of HVC, such as nucleus uvaeformis (Nottebohm et al., 1982; Ashmore et al., 2008).”

“In contrast, LMAN lesions or inactivation produce an increase in song stereotypy in plastic song and adult birds (Kao et al., 2005; Ölveczky et al., 2005).”

“…these neurons generate a sparse sequence of bursts (Hahnloser et al., 2002; Kozhevnikov and Fee, 2007; Long et al., 2010) that is thought to arise from a synaptically connected chain of neuronal groups (Abeles, 1991; Vogels et al., 2005; Li and Greenside, 2006; Jin et al., 2007; Long et al., 2010).”

“Gradually, during the “plastic-song” stage, vocalizations become more stereotyped until, in adult- hood, singing consists of a highly precise sequence of syllables and silent gaps (Tchernichovski et al., 2001; Glaze and Troyer, 2006).”

“To remove waste heat generated by current flow through the device (Long and Fee, 2008; Aronov and Fee, 2011), a convective coppermesh heat sink was attached to the hot plate of the device.”

“…these neurons generate a sparse sequence of bursts (Hahnloser et al., 2002; Kozhevnikov and Fee, 2007; Long et al., 2010) that is thought to arise from a synaptically connected chain of neuronal groups (Abeles, 1991; Vogels et al., 2005; Li and Greenside, 2006; Jin et al., 2007; Long et al., 2010).”

“A key “cortical” area for mature singing is HVC (used as a proper name) (Nottebohm et al., 1976; Simpson and Vicario, 1990; Yu and Margoliash, 1996; Hahnloser et al., 2002).”

“Specifically, LMAN receives input from the medial part of the dorsolateral thalamus (DLM), which in turn receives inputs from a basal ganglia nucleus Area X (Okuhata and Saito, 1987; Bottjer et al., 1989; Luo and Perkel, 1999).”

“, 2008; Stepanek and Doupe, 2010 trial-and-error learning (Doya and Sejnowski, 1995; Tumer and Brainard, 2007; Andalman and Fee, 2009).”

“At an early learning stage, they produce subsong: highly variable vocalizations similar to human babbling (Marler, 1970; Oller et al., 1976; Doupe and Kuhl, 1999).”

“Thus, we modeled the duration distribution of mode-3 gaps as a sum of a Gaussian-distributed variable and an exponential-distributed variable, forming an exGaussian distribution (Hohle, 1965).”

“…thought to form under the influence of local learning rules (Miller, 1996), it is possible that distinct forms of circuit dynamics—such as stereotyped neuronal sequences or stochastic patterns—similarly result from the application of simple learning rules (Jun and Jin, 2007; Fiete et al., 2010).”

“Consistent with this idea, single-neuron recordings in LMAN suggest that this area is active throughout subsong (Aronov et al., 2008), plastic song (Ölveczky et al., 2005), and even adult song (Kao and Brainard, 2006).”

“, 2011) or even by peripheral mechanisms of song production (Fee et al., 1998; Goller and Cooper, 2004; Riede and Goller, 2010).”

“…a brief burst of spikes at one moment in the song, and, as a population, these neurons generate a sparse sequence of bursts (Hahnloser et al., 2002; Kozhevnikov and Fee, 2007; Long et al., 2010) that is thought to arise from a synaptically connected chain of neuronal groups (Abeles, 1991; Vogels…”

“LMAN is reciprocally interconnected with other brain areas as part of a basal ganglia–forebrain loop (Farries and Perkel, 2002; Person et al., 2008; Gale and Perkel, 2010).”

“DOI:10.1523/JNEUROSCI.3009-11.2011 Copyright © 2011 the authors 0270-6474/11/3116353-16$15.00/0 necessary feature for exploration in; kao et al., 2008; Stepanek and Doupe, 2010 trial-and-error learning (Doya and Sejnowski, 1995; Tumer and Brainard, 2007; Andalman and Fee, 2009).”

“Protogaps became increasingly common during development, perhaps arising from an increasing coordination between vocalizations and respiration (Veit et al., 2011) that eventually leads to the precise coordination of these processes in adult song (Hartley and Suthers, 1989; Franz and Goller, 2002).”

“, 2011) or even by peripheral mechanisms of song production (Fee et al., 1998; Goller and Cooper, 2004; Riede and Goller, 2010).”

“Gradually, during the “plastic-song” stage, vocalizations become more stereotyped until, in adult- hood, singing consists of a highly precise sequence of syllables and silent gaps (Tchernichovski et al., 2001; Glaze and Troyer, 2006).”

“Specifically, LMAN receives input from the medial part of the dorsolateral thalamus (DLM), which in turn receives inputs from a basal ganglia nucleus Area X (Okuhata and Saito, 1987; Bottjer et al., 1989; Luo and Perkel, 1999).”

“LMAN is reciprocally interconnected with other brain areas as part of a basal ganglia–forebrain loop (Farries and Perkel, 2002; Person et al., 2008; Gale and Perkel, 2010).”

“HVC projects to RA (robust nucleus of the arcopallium), which in turn projects to brainstem vocal and respiratory nuclei (Wild, 2004).”

“Air sac pressure measurements during subsong production were performed using methods similar to those described previously for adult birds (Franz and Goller, 2002; Goller and Cooper, 2004).”

“LMAN is the “cortical” output stage of an avian basal– ganglia– thalamocortical loop (Perkel et al., 2002; Farries et al., 2005) which, like HVC, also projects to RA (Bottjer et al.”

“…older birds, syllable durations deviated from an exponential distribution because of the appearance of consistently timed syllables during the early plastic-song phase (Liu et al., 2004; Tchernichovski et al., 2004; Aronov et al., 2008); these syllables formed peaks in duration distributions (Fig.”

“During later developmental stages, LMAN continues to contribute to song production by introducing variability to singing (Kao et al., 2005, 2008; Ölveczky et al., 2005; Stepanek and Doupe, 2010), a Received June 14, 2011; revised Sept.”

“…these neurons generate a sparse sequence of bursts (Hahnloser et al., 2002; Kozhevnikov and Fee, 2007; Long et al., 2010) that is thought to arise from a synaptically connected chain of neuronal groups (Abeles, 1991; Vogels et al., 2005; Li and Greenside, 2006; Jin et al., 2007; Long et al., 2010).”

“…thought to form under the influence of local learning rules (Miller, 1996), it is possible that distinct forms of circuit dynamics—such as stereotyped neuronal sequences or stochastic patterns—similarly result from the application of simple learning rules (Jun and Jin, 2007; Fiete et al., 2010).”

“LMAN is reciprocally interconnected with other brain areas as part of a basal ganglia–forebrain loop (Farries and Perkel, 2002; Person et al., 2008; Gale and Perkel, 2010).”

“Recent work has shown that lesions of DLM mostly eliminate vocal variability in young birds, whereas lesions of Area X have little effect on variability (Goldberg and Fee, 2011), suggesting that DLM plays a key role in generating subsong vocalizations.”

“Air sac pressure measurements during subsong production were performed using methods similar to those described previously for adult birds (Franz and Goller, 2002; Goller and Cooper, 2004).”

“…these neurons generate a sparse sequence of bursts (Hahnloser et al., 2002; Kozhevnikov and Fee, 2007; Long et al., 2010) that is thought to arise from a synaptically connected chain of neuronal groups (Abeles, 1991; Vogels et al., 2005; Li and Greenside, 2006; Jin et al., 2007; Long et al., 2010).”

“HVC receives feedback connections from RA via a pathway through the midbrain and thalamus (Schmidt et al., 2004; Ashmore et al., 2008).”

“Some finer aspects of timing in the subsyllabic acoustic or respiratory structure may be influenced by areas downstream of HVC and LMAN (Andalman et al., 2011) or even by peripheral mechanisms of song production (Fee et al.”

“…older birds, syllable durations deviated from an exponential distribution because of the appearance of consistently timed syllables during the early plastic-song phase (Liu et al., 2004; Tchernichovski et al., 2004; Aronov et al., 2008); these syllables formed peaks in duration distributions (Fig.”

“HVC receives feedback connections from RA via a pathway through the midbrain and thalamus (Schmidt et al., 2004; Ashmore et al., 2008).”

“How might the LMAN- and HVC-dependent modes we identified interact during early song development? We found that protosyllables and protogaps tend to follow one another, perhaps accounting for the previously described early appearance of rhythmicity in singing (Saar and Mitra, 2008).”

“Furthermore, just as cortical properties such as maps and receptive fields are thought to form under the influence of local learning rules (Miller, 1996), it is possible that distinct forms of circuit dynamics—such as stereotyped neuronal sequences or stochastic patterns—similarly result from the…”

“Early singing is characterized by two distinct modes of timing Characterizing the temporal structure of a behavior is necessary to understand how the brain learns and generates the timing of behavioral sequences (Lipkind and Tchernichovski, 2011).”

“As described in detail previously (Veit et al., 2011), in birds of all ages, even the youngest recorded ( 40 dph), the distribution of song amplitudes exhibited a bimodal shape, with two peaks corresponding to vocalization and silence (Fig.”

“To remove waste heat generated by current flow through the device (Long and Fee, 2008; Aronov and Fee, 2011), a convective coppermesh heat sink was attached to the hot plate of the device.”

“Because sequences of protosyllables and protogaps developmentally transform into adult song motifs (Tchernichovski et al., 2001; Tchernichovski and Mitra, 2002), these results suggest that the biophysical processes within HVC controlling the timing of early song elements may be related to those controlling the timing…”

“LMAN is the “cortical” output stage of an avian basal– ganglia– thalamocortical loop (Perkel et al., 2002; Farries et al., 2005) which, like HVC, also projects to RA (Bottjer et al.”

“Because temperature affects the speed of all cellular processes, this result suggests that the neural dynamics generated by intrinsic circuitry within HVC control song timing in adulthood (Long and Fee, 2008; Fee and Long, 2011).”

“Temperature in the brain is strongly dependent on the distance from the cooling or heating probe (Jafari and Higgins, 1989; Long and Fee, 2008).”

“More recently, it has been found that localized cooling f LMAN in very young birds slows down the timescales of ubsong babbling, suggesting that neuronal or circuit dyamics within LMAN may play a direct role in the generaion of vocal variability (Aronov et al., 2011).”

“…birdsong learning is driven by reinforcement learning using a specialized cost function that relies on comparison with a memorized version of a tutor’s song (Fiete et al., 2007), and also that it involves specialized structures for controlling song variability during learning (Aronov et al., 2011).”

“Spectral Analysis of Song Amplitude and Spike Trains Song amplitude was calculated as previously described (Aronov et al., 2011).”

“The discrepancy of our results with the previous study of Cooper & Goller (2006) may be due to the fact that gaps and syllables do not simply reflect inspiration and expiration, respectively (Aronov et al., 2011).”

“It is now possible to track trajectories of vocal changes leading to imitation continuously over development [6 ], and to identify the emergence of syllable types and the differentiation of prototype syllables [6 ,7].”

“, 1994), localized cooling (Long and Fee, 2008; Aronov et al., 2011), and single cell recordings (Hahnloser et al.”

“Furthermore, local brain cooling within LMAN results in slowing of the characteristic timescales of vocal babbling, suggesting that the biophysical and circuit dynamics within LMAN are involved in generating vocal variability (Aronov et al., 2011).”

“Several studies of the zebra finch song have reported the differentiation of syllable types [7] and broad unimodal distributions of syllables and silent gaps during early development [12].”

“Syllables and gaps were segmented based on the analysis described by Aronov et al., 2011.”

“Hence in the fictive singing paradigm, the muscles of the syrinx are articulated by multi-channel stimulation of the nXIIts while the respiratory system is pressurized to levels typical of normal singing (Aronov et al., 2011) by a cannula placed in the abdominal airsac (Brown and Pilny, 2006) (Figure 5d).”

“Area X can exert a strong, precisely timed influence on LMAN via DLM (50, 51, 60, 61).”

“This idea is consistent with a report that basal ganglia–thalamocortical circuits, including Area X, are required for the generation of the random mode producing broadly distributed durations of syllables and inter-syllables (Aronov et al., 2011).”

“For example, because intersyllable gaps coincide with short inspirations during song (Aronov et al. 2011; reviewed in Goller and Cooper 2004; Veit et al. 2011), the shortening of gaps could indicate that birds are more efficient at replenishing their air supply with shorter inspirations.”

“The HVC is involved in the con-trol of stereotyped song timing [7,8] and processing of syntactic information [9].”

“…and timing (Vu et al., 1994; Yu and Margoliash, 1996; Schmidt, 2003; Ashmore et al., 2005; Thompson and Johnson, 2007; Long and Fee, 2008; Sakata and Brainard, 2008; Wang et al., 2008; reviewed in Jin, 2009; Aronov et al., 2011; Fujimoto et al., 2011; Rajan and Doupe, 2013; Basista et al., 2014).”

“For comparison, the light gray bar indicates the range of proto-syllable durations and the light gray circle indicates the mean duration of proto-syllables in juvenile zebra finches.(32)”

“As birds progress to the plastic song phase, they produce more regular syllable types which begin to appear as peaks in the distribution of syllable durations, and therefore are no longer well-fit by an exponential (Aronov et al., 2011; Tchernichovski et al., 2004).”

“However, the syllables of blocked birds exhibited duration distributions with few peaks and shapes that more closely resembled the distributions of juvenile birds (Fig. 4B; see Fig. 2, B and G, for juvenile distributions; Aronov et al. 2011; Tchernichovski et al. 2001).”

“Protosyl- lables are the first vocal sounds driven primarily by the posterior pathway (Aronov et al., 2008, 2011) and our results suggest that protosyllables remain in a largely undifferentiated state when LMAN ablation occurs before their production or differentiation.”

“In several vertebrates, precisely timed sequences of behaviour are not innate but are acquired by juvenile animals (Aronov, Veit, Goldberg, & Fee, 2011).”

“Over the next 50 days, the song gradually becomes more stereotyped and similar to the tutor song, finally crystalizing by 90-100 dph [25, 26].”

“In juve-niles, HVC lesions result in the abolition of adult like gap and syllable durations and HVC cooling in adults results in an elongation of syllables and gaps [13].”

“As shown previously, the temporal structure of zebra finch songs becomes increasingly stereotyped during the sensory-motor phase of development 37,38 .”