THE PHYSIOLOGICAL SOCIETY,
Trinity College Dublin Meeting,
24th to 26th March 1997, Dublin.
When are class I mGluRs nessecary for hippocampal LTP?
Thomas Behnisch, Volker Wilsch, Tino Jaeger, Klaus G. Reymann
and Detlef Balschun (introduced by J.J. O'Connor)
Long term potentialtion (LTP) is an activity-dependent form
of synaptic plasticity which can be observed as a model of
the cellular mechanisms underlying learning and memory.
In the hippocampus, where LTP has been most intensively studied,
its induction was proven to require the influx of calcium through
N-methyl-D-aspartate (NMDA) type of glutamate receptors under
most experimental conditions. However, since an activation of NMDA
receptors alone resulted in a short-term potentiation other
mechanisms have been suggested to be involved. In particular,
the involvement of metabotropic glutamate receptors (mGluRs) in
hippocampal LTP ia a matter of controversial debate. We report
here, that the efficacy of the broad-spectrum mGluR antagonist
(S)-(a)-methyl-4-carboxyphenylglycine (MCPG, 400 µM) and of
4-carboxyphenylglycine (4-CPG, 100 µM), a selective
antagonist at class I mGluRs, in LTP is contingent upon the
tetanization strength and the resulting [Ca2+]i response.
As indicated by experiments in which we blocked voltage-dependent
calcium channels (VDCCs) and intracellular calcium stores (ICSs)
using nimodipine (10 µM) and thapsigargin (20 µM), respectively,
the functional significance of class I mGluRs in LTP is confined
to certain types of potentiation that are induced by weak
tetanization protocols and which require the release of Ca2+
from ICSs for induction. During strong tetanic stimulation
this Ca2+ route is functionally bypassed by VDCCs, resulting in
a potentiation which is not suspectible to the action of MCPG
and 4-CPG. Therefore, we suggest, that the different paths
for intracellular calcium increase can be substituted against
each other in dependence of the employed tetanization strength.
Back to My job
Feel free to  |
me! jaeger@ifn-magdeburg.de |