Basal ganglia output to the thalamus: still a paradox.

The basal ganglia (BG)-recipient thalamus controls motor output but it remains unclear how its activity is regulated. Several studies report that thalamic activation occurs via disinhibition during pauses in the firing of inhibitory pallidal inputs from the BG. Other studies indicate that thalamic spiking is triggered by pallidal inputs via post-inhibitory 'rebound' calcium spikes. Finally excitatory cortical inputs can drive thalamic activity, which becomes entrained, or time-locked, to pallidal spikes. We present a unifying framework where these seemingly distinct results arise from a continuum of thalamic firing 'modes' controlled by excitatory inputs. We provide a mechanistic explanation for paradoxical pallidothalamic coactivations observed during behavior that raises new questions about what information is integrated in the thalamus to control behavior.

Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds.

The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (∼5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory "rebound" mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as "gating" of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel "entrainment" mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission--rebound, gating, and entrainment--depending on the amount of excitation the thalamic neuron receives.

A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds.

The pallido-recipient thalamus transmits information from the basal ganglia to the cortex and is critical for motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the basal ganglia, but the role of nonpallidal inputs, such as excitatory inputs from cortex, remains unclear. We simultaneously recorded from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a basal ganglia-recipient thalamic nucleus that is necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor cortical nucleus that is also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals that are important for exploratory behavior and learning.

Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia.

Young songbirds produce vocal "babbling," and the variability of their songs is thought to underlie a process of trial-and-error vocal learning. It is known that this exploratory variability requires the "cortical" component of a basal ganglia (BG) thalamocortical loop, but less understood is the role of the BG and thalamic components in this behavior. We found that large bilateral lesions to the songbird BG homolog Area X had little or no effect on song variability during vocal babbling. In contrast, lesions to the BG-recipient thalamic nucleus DLM (medial portion of the dorsolateral thalamus) largely abolished normal vocal babbling in young birds and caused a dramatic increase in song stereotypy. These findings support the idea that the motor thalamus plays a key role in the expression of exploratory juvenile behaviors during learning.

Singing-related activity of identified HVC neurons in the zebra finch.

High vocal center (HVC) is part of the premotor pathway necessary for song production and is also a primary source of input to the anterior forebrain pathway (AFP), a basal ganglia-related circuit essential for vocal learning. We have examined the activity of identified HVC neurons of zebra finches during singing. Antidromic activation was used to identify three classes of HVC cells: neurons projecting to the premotor nucleus RA, neurons projecting to area X in the AFP, and putative HVC interneurons. HVC interneurons are active throughout the song and display tonic patterns of activity. Projection neurons exhibit highly phasic stereotyped firing patterns. X-projecting (HVC((X))) neurons burst zero to four times per motif, whereas RA-projecting neurons burst extremely sparsely--at most once per motif. The bursts of HVC projection neurons are tightly locked to the song and typically have a jitter of <1 ms. Population activity of interneurons, but not projection neurons, was significantly correlated with syllable patterns. Consistent with the idea that HVC codes for the temporal order in the song rather than for sound, the vocal dynamics and neural dynamics in HVC occur on different and uncorrelated time scales. We test whether HVC((X)) neurons are auditory sensitive during singing. We recorded the activity of these neurons in juvenile birds during singing and found that firing patterns of these neurons are not altered by distorted auditory feedback, which is known to disrupt learning or to cause degradation of song already learned.

Measurement of the linear and nonlinear mechanical properties of the oscine syrinx: implications for function.

We have measured the vibrational modes of the sound producing membrane in the syrinx of zebra finches and canaries. Excised syringes were driven with a frequency-swept acoustic pressure wave through the trachea, and the resulting vibrations measured using a laser interferometer. The frequency-dependent membrane compliance was measured at 10-20 different positions, giving a detailed picture of the linear vibrational modes of the two membrane components, the medial labium and the medial tympaniform membrane. Nonlinear properties of the membrane were determined by measuring the linear response at several superimposed static pressures. The membrane compliance is dominated by the lowest vibrational mode, a narrow mechanical resonance, at roughly 700 Hz in the zebra finch, that extends over the entire membrane. Several higher-frequency modes were also observed. The frequency of the lowest vibrational mode is determined largely by the mass of the heavier medial labium, rather than the thinner medial tympaniform membrane, suggesting that the medial labium is critical in determining the oscillatory frequency of the syrinx. The difference in mass of the medial labium and medial tympaniform membrane may serve to produce a wave-like motion of the membranes during flow-driven oscillations, thus increasing the efficiency of sound production. Implications for mechanisms of frequency tuning are discussed.