Role of Muscarinic Cholinergic Neurotransmission in CA1 synapses of rat hippocampus

VICTORIA OBERHOLZER; CARLOS CERVEÑANSKY; DIANA JERUSALINSKY; EDGAR KORNISIUK

Montevideo, Uruguay

Taller; Escuela de Neurociencias IBRO de MVD; 2009

IBRO-LARC

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Role of Muscarinic Cholinergic Neurotransmission in CA1 synapses of rat hippocampus   Victoria Oberholzer1,2, Carlos Cerveñansky3, Diana Jerusalinsky1,4 y Edgar Kornisiuk1. 1 LaN&N, IBCN, Univ. Bs. As. (UBA) & CONICET; 2 FCEN, UBA, Buenos Aires, Argentina; 3 UBioqA, IIB, Montevideo, Uruguay; 4 CBC, UBA. Buenos Aires, Argentina. vic.ober@gmail.com   Muscarinic antagonists produce amnesia while agonists produce facilitation of memory when injected into the dorsal hippocampus of the rat immediately after training in an inhibitory avoidance task. Muscarinic toxin MT2 from the Green Mamba venom is a selective M1 receptor agonist and a M4 receptor antagonist (with a four-fold lower affinity for M4). This toxin caused facilitation in an inhibitory avoidance task. We have demonstrated that MT3, the most selective M4 antagonist known, inhibited long term potentiation (LTP) induced by high frequency stimulation, as revealed in field potential recordings of the CA1 synapses in rat hippocampal slices. The aim of this work was to characterize the muscarinic participation in neurotransmission in the CA1 region, either in basal conditions or after potentiation by a theta burst frequency stimulation protocol (TBS), by recording field potentials in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSP) were obtained by stimulating Schaffer collaterals and recording close to pyramidal cells dendrites (glutamatergic synapses) in the presence of atropine (non selective muscarinic antagonist), pirenzepine (selective M1 and M4 antagonist) and MT2. Maximum slopes of fEPSP were analysed and compared to control recordings. Pirenzepine 25 mM blocked LTP induction, without affecting basal transmission. On the other hand, 1 mM MT2 showed a facilitatory –though no lasting- effect (+ 50 ± 7 % over basal transmission) which was blocked by 25 mM pirenzepine. Atropine 10 mM also blocked facilitation by MT2. These and previously reported results show that both M1 and M4 receptors appear positively involved in LTP induction by TFS and that the M1 receptor subtype positively modulates basal transmission in the CA1 region.     Key words: muscarinic acetylcholine receptor • CA1 synapses • long-term potentiation • rat hippocampus • muscarinic toxin MT2