Talk abstract:
Ionic Conductances Regulating the Discharge
Patterns
of Cochlear Nucleus Neurons
Paul B. Manis
Associate Professor
Otolaryngology-Head and Neck Surgery
Johns Hopkins University School of Medicine
420 Ross Res. Bldg.
720 Rutland Ave
Baltimore, MD 21205
pmanis@bme.jhu.edu
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.)
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1998-1999
Mathematics in Biology