IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
M1 Muscarinic Acetylcholine Receptor is required for LTP induction at CA1 synapses of rat hippocampus
Autor/es:
OBERHOLZER, MARÍA VICTORIA; GONZÁLEZ, NICOLÁS; KORNISIUK, EDGAR; SERVENT DENIS; CERVEÑANSKY, CARLOS; JERUSALINSKY, DIANA
Lugar:
Buenos Aires
Reunión:
Simposio; 2° Simposio Franco-Argentino de Neurociencias; 2012
Resumen:
P { margin-bottom: 0.21cm; }
Muscarinic
cholinergic modulation of neurotransmission in rat hippocampus has
been recurrently documented in several works, though the involvement
of the different receptor subtypes has not been completely
characterized. Muscarinic toxins (MTs) 1 and 2 from Dendroaspis
angusticeps
snake venom act as selective M1
receptor agonists and M4
antagonists. MT2 has 4-fold higher affinity for M1
than for M4
receptor. Both toxins enhanced field potentials (fEPSP) at CA1
synapses in rat hippocampal fresh slices. This MT2 enhancement of
fEPSP was effectively blocked by both atropine (specific though
non-selective muscarinic antagonist) and pirenzepine (selective
antagonist for M1
and
M4
receptors), strongly suggesting the M1
receptor involvement in the phenomenon. Furthermore,
N-methyl-scopolamine (NMS, specific non-selective antagonist) and
pirenzepine blocked LTP induction by theta burst stimulation
(TBS-LTP) in the same synapses. We used MT7, the most selective M1
antagonist known, to elucidate if the effect of MT1 and MT2 on fEPSP
recorded at CA1 synapses was mediated through M1
receptor subtype and whether it was the blockade of this receptor by
classical muscarinic antagonists the direct responsible for TBS-LTP
inhibition. MT7 (10 nM) completely abolished MT1 and MT2-induced
increases in fEPSP and TBS-LTP induction.Taking into account that
both MT1 and MT2 have significant affinities for α-adrenergic
receptors, and that the α-adrenergic
antagonist prazosin (PRZ) and the agonist phenylephrine also
modified fEPSPs, we performed radioligand binding assays in rat
hippocampal synaptosomal membranes to evaluate MT7 inhibition of
both 3H-NMS
and 3H-PRZ
binding. MT7 inhibited 3H-NMS
binding but did not inhibit 3H-PRZ
binding. Moreover, maximal inhibition of 3H-NMS
binding was 38 ± 5%, close to M1
ratio in rat hippocampus. These
results demonstrate that M1
muscarinic receptors positively modulate basal transmission and that
they are required for LTP induction by TBS at CA1 synapses.