Basal ganglia function, stuttering, sequencing and repair in adult songbirds

Abstract

A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

Human mutant huntingtin disrupts vocal learning in transgenic songbirds

“…Thus, we suspect that the tapering of song deterioration may occur after the most vulnerable neurons (MSNs) have died and are subsequently replaced by migrating newborn neurons. Adult zebra finches are known to continuously recruit new MSNs to the basal ganglia nucleus Area X 34 , and adult neurogenesis in song nuclei is functionally associated with the maintenance of song stability 35,36 . If the recruitment of new neurons contributes to the stabilization of mutant song, song degradation would be expected to occur again later in life.…”

Dopamine D3 receptors modulate the rate of neuronal recovery, cell recruitment in Area X, and song tempo after neurotoxic damage in songbirds

“…27 Striatal neurogenesis following brain injury in rodents 28 is limited and most of the newly formed neurons in 29 striatum do not survive 6 weeks (Arvidsson et al, 2002; 30 Thored et al, 2006). On the other hand, there is a sub-31 stantial regeneration of striatal vocal nucleus lateral Area 32 X (LArea X; the distinction between lateral and medial 33 Area X shown in Kubikova et al, 2007) lasting at least 34 for 6 months after neurotoxic injury in songbirds with high-35 est recovery within the first month and neurons being inte-36 grated into the neural circuits (Kubikova et al, 2014). The 37 nucleus Area X is necessary for song learning in juveniles 38 (Scharff and Nottebohm, 1991) and affects also song The main experiment consisted of surgery with bilateral neurotoxic LArea X lesion and subcutaneous implantation of osmotic minipump containing 7-OH-DPAT, U99194, or NaCl.…”

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

“…The songrelated effects of expressing mHTT in area X exert selective behavioral and anatomical effects that contrast with the behavioral and anatomical effects elicited by area X lesions, thus helping to illuminate how different components of the BG circuitry regulate sequential movements. First, sequence variability, vocal activity, and song bout duration increase in mHTT finches but are often unaffected following area X lesions in adult birds (36,37; but see 38,39). Moreover, variability and duration of individual syllables are unaffected in mHTT birds but are altered following area X lesions (30,38).…”

“…First, sequence variability, vocal activity, and song bout duration increase in mHTT finches but are often unaffected following area X lesions in adult birds (36,37; but see 38,39). Moreover, variability and duration of individual syllables are unaffected in mHTT birds but are altered following area X lesions (30,38). The song behavior of mHTT birds could not simply be attributed to nonspecific cytotoxic effects of viral injection, infection, or overexpression of mHTT, because expressing exon 1 with 20 CAG repeats [i.e., a quantity fivefold greater than the avian repeat number (23)] was without any discernible behavioral effect.…”

“…One consequence of MSN cell death is the marked reduction of inhibitory puncta on DLM-projecting pallidal neuron cell bodies and proximal dendrites, which presumably reflects the loss of inhibitory input from MSNs, and perhaps from other inhibitory neurons in area X. Although syllable repetitions in zebra finches with area X lesions have been speculated to arise from the replacement of MSNs through ongoing neurogenesis (38), the persistent reduction in inhibitory synapses on the DLM-projecting pallidal neurons we observed suggests that the primary factor driving abnormal vocal behavior is the massive loss of MSNs, which is a hallmark of HD. Ultimately, because pallidal neurons fire action potentials spontaneously and at high rates, and because MSN neurons generate precisely timed action potential bursts during singing (13), this loss of MSN input is likely to diminish or otherwise alter precisely timed singing-related activity in pallidal neurons.…”