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Blockade of M2‐like muscarinic receptors enhances long‐term potentiation at corticostriatal synapses
Author(s) -
Calabresi Paolo,
Centonze Diego,
Gubellini Paolo,
Pisani Antonio,
Bernardi Giorgio
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1998.00348.x
Subject(s) - methoctramine , long term potentiation , long term depression , muscarinic acetylcholine receptor , neuroscience , chemistry , postsynaptic potential , muscarinic acetylcholine receptor m4 , excitatory postsynaptic potential , muscarinic acetylcholine receptor m2 , synaptic plasticity , oxotremorine , cnqx , nmda receptor , ampa receptor , biology , inhibitory postsynaptic potential , receptor , biochemistry
Acetylcholine (ACh) exerts a crucial role in learning and memory. The striatum contains the highest concentration of this transmitter in the brain. This structure expresses two different forms of synaptic plasticity, long‐term depression (LTD) and long‐term potentiation (LTP), which might contribute to the storage of motor skills and some cognitive processes. We have investigated the role of M2‐like muscarinic receptors in striatal LTP by utilizing intracellular recordings in vitro from a rat corticostriatal slice preparation. Methoctramine (250 n m ), an antagonist of M2‐like muscarinic receptors, enhanced striatal LTP induced in the absence of external magnesium (Mg 2+ ) by high‐frequency stimulation (HFS) of corticostriatal fibres. Methoctramine did not affect the amplitude of excitatory postsynaptic potentials (EPSPs) when bath applied either before or after the conditioning tetanus suggesting that a critical increase of ACh concentrations is produced only during HFS. Methoctramine per se failed to enhance the NMDA‐mediated EPSPs recorded in the absence of external Mg 2+ and in the presence of 10 μ m CNQX. Methoctramine antagonized the presynaptic inhibitory action of neostigmine, an inhibitor of ACh‐esterase, and oxotremorine, an agonist of M2‐like muscarinic receptors. These data indicate that the activation of M2‐like muscarinic receptors exerts a negative influence on striatal LTP, probably by reducing the release of glutamate from corticostriatal fibres and they suggest a complex modulatory effect of ACh in striatal synaptic plasticity.