M4 muscarinic receptors are involved in modulation of neurotransmission at synapses of Schaffer collaterals on CA1 hippocampal neurons in rats.

GONZALO SÁNCHEZ; LUCAS DE OLIVEIRA ALVARES; VICTORIA OBERHOLZER; BRUNA GENRO; JORGE QUILLFELDT; JADERSON COSTA DA COSTA; CARLOS CERVEÑANSKY; DIANA JERUSALINSKY; EDGAR KORNISIUK

JOURNAL OF NEUROSCIENCE RESEARCH

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2009 p. 691 - 700

0360-4012

All five subtypes of muscarinic acetylcholine receptors (mAChR) (M1-M5) areexpressed in the hippocampus, where they are considered to be involved both incognitive functions and in synaptic plasticity such as long-term potentiation.Muscarinic toxins (MTs) are small proteins from mamba snake venoms thatdisplay exquisite discrimination between mAChRs. MT1 acts as agonist at M1 andantagonist at M4 receptors, with similar affinities for both. MT3, the most selectiveantagonist available for M4 receptors, infused into CA1 region immediately after trainingcaused amnesia in the rat, indicating the participation of M4 receptors in memoryconsolidation.Our goal was to investigate the participation of M4 receptor in neurotransmissionat the hippocampal Schaffer collaterals-CA1 synapses. Two different preparations wereused: 1. field potential recordings in freshly prepared rat hippocampal slices, with highfrequency stimulation and 2. whole-cell voltage-clamp in cultured hippocampalorganotypic slices, with paired stimuli. In preparation 1, a dose of MT3 which waspreviously shown to cause amnesia blocked LTP; the non-selective antagonistscopolamine blocked LTP without affecting basal transmission. In preparation 2, basaltransmission was decreased and induction of LTP was prevented by an MT3concentration that would bind mainly to M4 receptors.Although M1 receptors appeared to positively modulate transmission at theseexcitatory synapses, M1 activation concomitant with M4 blockade (by MT1), only alloweda brief short-term potentiation. Accordingly, M4 blockade by MT3 strongly supports apermissive role of M4 receptors and suggest their necessary participation in synapticplasticity at these synapses.Page 2 of 29Journal of Neuroscience Research