Recurrent Interactions between the Input and Output of a Songbird Cortico-Basal Ganglia Pathway Are Implicated in Vocal Sequence Variability

Abstract

Complex brain functions, such as the capacity to learn and modulate vocal sequences, depend on activity propagation in highly distributed neural networks. To explore the synaptic basis of activity propagation in such networks, we made dual in vivo intracellular recordings in anesthetized zebra finches from the input (nucleus HVC) and output (lateral magnocellular nucleus of the anterior nidopallium (LMAN)) neurons of a songbird cortico-basal ganglia (BG) pathway necessary to the learning and modulation of vocal motor sequences. These recordings reveal evidence of bidirectional interactions, rather than only feedforward propagation of activity from HVC to LMAN, as had been previously supposed. A combination of dual and triple recording configurations and pharmacological manipulations was used to map out circuitry by which activity propagates from LMAN to HVC. These experiments indicate that activity travels to HVC through at least two independent ipsilateral pathways, one of which involves fast signaling through a midbrain dopaminergic cell group, reminiscent of recurrent mesocortical loops described in mammals. We then used in vivo pharmacological manipulations to establish that augmented LMAN activity is sufficient to restore high levels of sequence variability in adult birds, suggesting that recurrent interactions through highly distributed forebrain – midbrain pathways can modulate learned vocal sequences.

Vocal motor changes beyond the sensitive period for song plasticity

“…Although there exists some evidence that the AFP can influence syllable sequencing and timing (e.g., Brainard and Doupe 2001; Goldberg and Fee 2011;Hamaguchi and Mooney 2012;Ölveczky et al 2005;Scharff and Nottebohm 1991;Thompson et al 2011), we argue that the AFP is not the primary locus of adult vocal change in Bengalese finches because studies documenting AFP influences on syllable sequencing and timing also observe AFP influences on syllable structure. For example, infusions of bicuculline into LMAN increase the variability of syllable sequencing as well as the spectral entropy of individual song syllables in adult zebra finches (Hamaguchi and Mooney 2012), and inactivations of LMAN decrease sequence variability as well as the variability of syllable structure in juvenile zebra finches (Ölveczky et al 2005). Because we did not observe significant changes to the variability of syllable structure in adult Bengalese finches, our findings are inconsistent with the model that the AFP drives agedependent changes to Bengalese finch song.…”

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

“…Although LMAN is not a layered structure with classic pyramidal cells, it shares many anatomic and physiologic similarities with the mammalian prefrontal cortex: LMAN lies anterior to motor and premotor areas, receives input from a dorsal thalamic nucleus that is not a primary sensory area, projects to the basal ganglia and to the primary song motor nucleus RA, and is more densely innervated by dopaminergic fibers than the region surrounding it (31,(60)(61)(62). Moreover, as with the prefrontal cortex, stimulation of LMAN does not evoke motor (song) output (24,46,63). Alternatively, or in addition, with respect to the hypothesis that avian nuclei are homologous to mammalian cortical layers (11,12,64), LMAN shares some but not all of the features of layer II/III intracortically connecting neurons.…”

Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences

“…Similarly, birds expressing mHTT in area X exhibited sequencelevel changes to song, but the structure and variability of individual syllables remained unaffected. The lack of changes to previously learned syllables and the continued ability of mHTT birds to modulate variability as a function of social context further support a model in which the variability of individual syllables and of the sequences in which they occur are at least partly under independent control (16,35). A possible clinical parallel is that humans with HD often exhibit grammatical errors and can struggle to produce complex sentences, even though simple phonemic generation can be preserved (33).…”

“…However, another intriguing possibility is that abnormal activity patterns in LMAN disrupt syllable sequences by interfering with HVC activity. Indeed, a recent study revealed an indirect pathway from LMAN to HVC that includes area X, the ventral pallidum, and a midbrain cell group (A11) (16). In this view, temporally abnormal activity patterns in LMAN can promote the production of certain syllables at wrong times in the sequence by acutely altering premotor commands at the level of HVC (Fig.…”

“…More specifically, although pallidal neuron firing rates increased during song, the normal patterns of sharp and transient decreases in firing rate were absent, which could be accounted for by diminished inhibitory input from MSN cells. Notably, transient decreases in pallidal neuron firing rate are sufficient to generate action potential bursts in their postsynaptic targets in the song motor thalamus (i.e., DLM) (42), which, in turn, excite the LMAN neurons that are an important source of vocal variability (14,16,43). Therefore, expressing mHTT in area X has the potential to alter activity not only in the BG but also in the cortical neurons that are indirect targets of pallidal neurons and that more directly affect vocalization.…”