Steroid Effects on Neural Plasticity and Behavior
Research Interests
Neural Plasticity
Vocal Communication
Rhythmic Motor Patterns
Steroids and Cell Death
Metamorphosis
Vocal communication in the Plainfin midshipman, P. notatus
Vocal communication is a fundamental component of social interactions among all vertebrates and often essential for courtship and agonistic behaviors. The teleost vocal pattern generator represents the simplest vertebrate preparation for investigating the firing properties of discrete vocal control nuclei because vocalizations are robust, its identified neural circuit is uncoupled from other behaviors such as respiration, and it is an inate trait not dependent on learning and memory.
Current studies are testing the hypothesis that the electroresponsive properties of vocal neurons differ from non-vocal neurons and establish the temporal properties of the rhythmic vocal motor output that predicts the temporal features of natural vocalizations using whole-cell patch electrophysiology in an in vitro hindbrain-spinal slice preparation.
In response to sustained depolarization, vocal neuron action potentials quickly attenuate (upper trace) instead of firing tonically (lower trace, non-vocal neuron). However, vocal neurons have a greater peak firing frequency and can follow a suprathreshold, sinusoidal stimulus at high frequencies, much like that seen of natural calls (not shown).
Potassium channel block induces rhythmic activity in vocal neurons. Oscillations were rapidly and reversibly blocked by tetrodotoxin but were unaffected by synaptic transmission blockers.
GABA-immunoreactivity (red) is abundant in fibers and terminals throughout the vocal motor nucleus (labeled green via transneuronal biocytin transport). Smaller GABAergic neurons are located lateral to the nucleus (not shown). GABA rapidly and reversibly inhibited vocal neuron spikes although GABA antagonists did not increase firing.
Future directions will look at how steroid hormones modulate the intrinsic membrane properties of vocal neurons both developmentally (long-term) and physiologically (short-term). As in other seasonally breeding animals, vocalizations are greatly enhanced during the breeding season. Seasonal changes in the firing ability of vocal neurons may accompany the seasonal changes in the temporal encoding properties of the peripheral auditory system.
In other experiments, the mechanism of potassium blockade to induce oscillations in vocal neurons will be further examined. What specific channel ion channels might underlie vocal neuron rhythmicity? What modulatory inputs could result in changes in potassium conductance? Is this effect intrinsic to vocal neurons or may electrical coupling via gap junctions play a role?
Metamorphosis of the tobacco hornworm, Manduca sexta
Insect metamorphosis, such as a crawling, feeding larva transforming into a subterranean, quiescent pupa and then to an adult capable of flight and reproduction, involves substantial pruning and rewiring of identified neurons and neural circuits in order to accommodate these dramatic changes in body plan, musculature, and behavior. The neural remodeling is regulated by steroid hormones called ecdysteroids and at the larval to pupal transition, a subset of accessory planta retractor motoneurons and their target muscles, which control movements of the larval prolegs, undergo segment-specific programmed cell death. Surviving motoneurons are respecified for other functions during pupal life and their demise occurs shortly after adult emergence. The regulation of cell death by steroids is a well-characterized phenomenon during development of the nervous system and is implicated in neurodegenerative diseases.
Past in vitro work demonstrated that ecdysteroids have a neuroprotective effect on proleg motoneurons cultured prior to adult emergence. In vivo hormone extirpation and replacement experiments support this finding.
Dying proleg motoneurons showed a significant reduction in the amplitude of sustained potassium current thereby increasing the contribution of the transient potassium current (bottom traces vs non-dying top traces). Correspondingly, high potassium media was neuroprotective. Dying motoneurons also showed a significant reduction in cell capacitance while other biophysical properties remain stable.
In other experiments, the metamorphic fate of this proleg neuromuscular system was examined in another Lepidopteran species. In Bombyx mori, the domesticated silkworm, there was an anterioward shift in the survival pattern of proleg muscles which may be associated with its reduced wing phenotype. However, surviving Bombyx muscles are similarly respecified to a rhythmic pupal motor pattern to circulate hemolymph (EMG traces in the same abdominal segment).
Marchaterre
