Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 30 (3), 1027-37

A Basal Ganglia Pathway Drives Selective Auditory Responses in Songbird Dopaminergic Neurons via Disinhibition

Affiliations

A Basal Ganglia Pathway Drives Selective Auditory Responses in Songbird Dopaminergic Neurons via Disinhibition

Samuel D Gale et al. J Neurosci.

Abstract

Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to the bird's own song (BOS) than to other sounds, and area X is critical for these responses. Direct pharmacological modulation of area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song control regions to dopaminergic neurons involves a projection from area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that area X disinhibits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning.

Figures

Figure 1.
Figure 1.
A pathway from the song control regions to dopaminergic neurons. A, Schematic parasagittal view of the zebra finch brain. HVC (proper name) projects to the robust nucleus of the arcopallium (RA) to form a song motor pathway. A separate population of HVC neurons projects to the basal ganglia region area X of the AFP. Area X projects to DLM, which projects to the lateral magnocellular nucleus of the anterior nidopallium (LMAN). LMAN projects to RA and collaterals of these axons project back to area X. Collaterals of area X neurons that project to DLM form terminals in the VP, which projects to the SNc and VTA. The SNc and VTA contain dopaminergic neurons that project densely to area X and surrounding striatum, and sparsely to other forebrain regions including HVC and RA. B, Detail of the circuitry addressed in this study. Pallidal-like neurons in area X are GABAergic and project to both DLM (not shown) and VP. Multiple cell types and unknown microcircuitry in VP and SNc/VTA make it difficult to predict the functional consequence, if any, of area X output on VP and dopaminergic neurons (question marks). C, Data presented in Results support a model in which increased activity of area X pallidal-like neurons inhibits spontaneously active, inhibitory projection neurons in VP and thereby disinhibits dopaminergic neurons. Neuronal firing is represented by vertical ticks on a horizontal line.
Figure 2.
Figure 2.
Auditory responses to BOS, reversed BOS, and conspecific song in example cells. A, Area X. B, VP. C, SNc/VTA dopaminergic neuron. For each brain region and stimulus, we show a raster plot indicating spike times on each trial, the average firing rate across trials (see Materials and Methods), and an oscillogram representing the auditory stimulus.
Figure 3.
Figure 3.
Response strength and selectivity of all area X, VP, and SNc/VTA dopaminergic neurons recorded. A, For each area X neuron (n = 122 cells, 67 birds), mean response to BOS (y-axis) compared with the mean response to each of the five non-BOS stimuli (x-axis), which include reverse BOS (Rev; black circles), conspecific song (Con; red circles), heterospecific song (Het; green circles), amplitude-modulated noise (blue circles), and unmodulated noise (magenta circles), as indicated in C. Each cell contributes a row of five circles with the same y-axis value. The dashed line has slope unity. B, Cumulative probability distribution of d′ values (see Materials and Methods) for area X neurons comparing responses to BOS with responses to each of the non-BOS stimuli, indicated by different colored lines as labeled in D. C, Same as A for VP neurons (n = 13 cells, 7 birds). D, Same as B for VP neurons. Values of d′ for VP neurons were multiplied by −1 (see Materials and Methods). E, Same as A for SNc/VTA dopaminergic neurons (n = 34 cells, 18 birds). F, Same as B for SNc/VTA dopaminergic neurons.
Figure 4.
Figure 4.
Identification of dopaminergic neurons in the SNc/VTA by spike waveform and juxtacellular labeling. A, Overlaid waveforms of spikes from a dopaminergic neuron (thin black lines). The thick, red line is the average spike waveform. The green brackets indicate the spike duration as defined in Materials and Methods. B, Same as A for a nondopaminergic neuron. C, Image of a juxtacellularly labeled cell. D, The cell in C is TH immunopositive. Scale bars: C, D, 20 μm. E, Spontaneous firing rate and spike duration of all cells recorded in SNc/VTA. Cells that were juxtacellularly labeled and shown to be TH immunopositive are indicated with filled, magenta circles. Juxtacellularly labeled cells that were TH negative are shown with filled, green circles. Cells that were not labeled are shown with open circles. F, Similar to E except showing the subset of cells whose auditory responses were tested. Cells that had auditory responses are indicated by filled triangles, and cells that were not responsive are shown with open triangles.
Figure 5.
Figure 5.
Population response to BOS and response latency of area X, VP, and SNc/VTA dopaminergic neurons. A, Average firing rate (normalized to baseline) of area X (red), VP (green), and SNc/VTA dopaminergic neurons (blue) during BOS playback. Time is normalized to the duration of BOS (see Materials and Methods). B, Cumulative probability distribution of response latencies to BOS (left) for area X (n = 122), VP (n = 13), and SNc/VTA dopaminergic neurons (n = 34), or response latencies to noise (right; n = 97, area X; n = 9, VP; n = 19, SNc/VTA).
Figure 6.
Figure 6.
Response of area X, VP, and SNc/VTA dopaminergic neurons to electrical stimulation (stim) in HVC. A, Raster plot and PSTH for an area X neuron. Single-pulse electrical stimulation of HVC occurred at time 0. Missing spikes near time 0 are attributable to the stimulation artifact, which obscures any spikes that occur near that time. B, Same as A for a VP neuron from a different bird. C, Same as A and B for a dopaminergic neuron from a different bird. D, Average PSTH for all area X (n = 31 cells, 18 birds), VP (n = 10 cells, 5 birds), and SNc/VTA dopaminergic neurons (n = 2 cells, 2 birds).
Figure 7.
Figure 7.
Effects of NBQX/AP5 injection in area X on auditory responses of SNc/VTA dopaminergic neurons. A, Response of a dopaminergic neuron to BOS before NBQX/AP5 injection in area X (top), after NBQX/AP5 injection in area X (middle), and during the last BOS trials of the recording (bottom). B, Response of five dopaminergic neurons (from 4 birds) to BOS before and after NBQX/AP5 injection in area X. C, Response to BOS of five different dopaminergic neurons (from 4 birds) before and after vehicle injection in area X. D, Spontaneous firing rate of the dopaminergic neurons shown in B and C before and after NBQX/AP5 (circles) or vehicle (squares) injection in area X.
Figure 8.
Figure 8.
Effects of glutamate and GABA injection in area X on the spontaneous firing rate of area X and SNc/VTA dopaminergic neurons. A, Response of an area X neuron to glutamate injection in area X at time 0. B, Spontaneous firing rate of five area X neurons (from 3 birds) before and after glutamate injection in area X (see Materials and Methods). C, Response of a dopaminergic neuron to glutamate injection in area X at time 0. The cells shown in A and C were not recorded simultaneously. D, Spontaneous firing rate of eight dopaminergic neurons (from 4 birds) before and after glutamate injection in area X. E–H, Same as A–D but for GABA injection in area X. Area X, n = 4 cells, 2 birds (F). SNc/VTA, n = 5 cells, 5 birds (H). The cells shown in E and G were not recorded simultaneously.

Similar articles

See all similar articles

Cited by 38 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback