[Abstract Title]. - Society for Neuroscience

Poster
240. Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs
and Activity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 240.21/F3
Topic: B.10.c. Activity-dependent plasticity of intrinsic membrane properties
Title: Activity-dependent depression of the spike after-depolarization generates long-lasting
intrinsic plasticity in hippocampal CA3 pyramidal neurones
Authors: *J. T. BROWN, A. D. RANDALL;
MRC Ctr. Synaptic Plasticity, Univ. Bristol, Bristol, United Kingdom
Abstract: Intrinsic neuronal plasticity is the process by which the core excitability of neurones is
modified in response to a conditioning stimulus. Long-lasting forms of intrinsic plasticity have
the potential to substantially alter information processing in the CNS thereby producing a broad
range of functional consequences. CA3 pyramidal neurones in rat hippocampal slices exhibited a
diverse range of stimulus-driven action potential firing patterns, however all cells exhibit an
initial high frequency (~80-200 Hz) burst of spikes. In experiments performed in the presence of
pharmacological blockers of fast synaptic transmission we have identified conditioning stimuli
that generate long-term intrinsic plasticity in these cells. Both tonic and phasic periods of
depolarization to -14 mV in voltage clamp produced robust and long-lasting changes in a number
of facets of CA3 neurone excitability. The spike afterdepolarization (ADP) following a 2 nA, 2
ms current injection was substantially depressed by conditioning. This change was accompanied
by a substantial prolongation of the first inter-spike interval generated by longer depolarizing
current injections. These long-lasting changes to excitability were termed depolarisation-induced
plasticity (DIP). Having established that depolarisation applied in voltage clamp was capable of
inducing DIP, we sought to establish whether more physiological stimulation paradigms could
induce DIP. Short, high frequency burst of 2-4 action potentials, repeated at 5 or 10 Hz for 1
minute effectively induced DIP. This form of DIP was eliminated by the inclusion of BAPTA in
the recording pipette. The Kv7/KCNQ/M-channel blocker, XE991, completely eliminated
conditioning-induced depression of the ADP. Furthermore, the Kv7 channel opener, retigabine,
which under control conditions suppresses the ADP, was rendered inactive following the
induction of DIP. These data indicate that modulation of Kv7 channels plays a central role in this
novel form of long-lasting intrinsic plasticity. We have also established that activation of
mGluR1 by either an exogenous agonist or via glutamatergic synaptic activity induces longlasting
depression of the ADP and associated changes to firing patterns. Our findings represent
the first demonstration of long-term plastic modulation of hippocampal ADPs and may represent
a novel and important form of intrinsic plasticity.