Paul B. Manis
Otolaryngology-Head and Neck Surgery
Johns Hopkins University School of Medicine
420 Ross Res. Bldg.
720 Rutland Ave
Baltimore, MD 21205
Joint work with Jason S. Rothman, Patrick O. Kanold, and Scott C. Molitor.
Voltage- and ion-sensitive channels play a crucial role in determining the discharge patterns and integrative capabilities of neurons. The cochlear nucleus provides a particularly interesting system to examine the roles of ion channels in information processing. In this nucleus, different sets of ion channels, patterns of afferent innervation, and local synaptic circuits are employed by the cells to transform their inputs into a variety of different temporal output patterns. Some ion channels are highly expressed in auditory neurons, suggesting that they play specific and critical roles in acoustic processing. Bushy cells of the ventral cochlear nucleus have a low-threshold (active at rest), partially inactivating potassium conductance that appears to be important in limiting temporal summation of EPSPs. This conductance permits these cells to accurately report the timing of discharges in the afferent auditory nerve fibers, and under appropriate conditions, behave as detectors of coincident synaptic inputs. A similar conductance has been described in the avian nucleus magnocellularis (equivalent to mammalian cochlear nucleus) and in several other classes of cells in the auditory system where analysis or preservation of timing information is important, including octopus cells and the principal neurons of the medial nucleus of the trapezoid body. This class of potassium conductance also appears to be crucial for coincidence detection in binaural processing in the medial superior olive and avian nucleus laminaris. Other cells of the auditory system operate in a regime that permits temporal and spatial integration of inputs, without regard to fine temporal structure. Stellate cells also have a non-inactivating inward current that may help sustain repetitive discharge and integrate small synaptic inputs, and many stellate cells have transient potassium currents that modulate discharge rates. Pyramidal cells of the dorsal cochlear nucleus are known to discharge with different patterns depending on the previous history of activity, but which do not reflect the fine structure of the input. These discharge patterns occur as discrete, stimulus-dependent, firing modes. The patterns primarily are produced by a prominent rapidly inactivating potassium conductance. Three other conductances are also proposed to be critical for determining the responses of these cells: a slowly inactivating potassium conductance, a cation-selective hyperpolarization activated conductance, and a non- inactivating sodium conductance. It appears that the interactions between these conductances determines the temporal discharge patterns of the pyramidal cells. These cells may also possess the ability to modulate their discharge patterns or synaptic efficacy. In both pyramidal and cartwheel cells of the dorsal cochlear nucleus, action potentials retrogradely propagate into the dendrites, eliciting a calcium influx through dendritic voltage-gated calcium channels. Thus, a calcium signal is available at the sites of synaptic inputs, and may serve to modulate those synapses or nearby ion channels, raising the possibility that information processing by these cells can be dynamically regulated by ongoing activity.
(Supported by NIH grants R01 DC00425 and P60 DC00979.)