Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition

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Abstract
Neuropeptide Y (NPY), the most abundant peptide in mammalian CNS, has been shown to inhibit excitatory neurotransmission presynaptically at the stratum radiatum-CA1 synapse in the in vitro rat hippocampal slice. We examined the site and mechanism of this inhibition in a series of in vitro intra- and extracellular recordings in areas CA1 and CA3, the source of much of the excitatory synaptic input to the CA1 neurons. NPY's inhibitory action at the stratum radiatum-CA1 synapse was unaffected by high concentrations of the antagonists bicuculline, theophylline, or atropine, suggesting that it does not act by stimulating the release of the known presynaptic inhibitory transmitters GABA, adenosine, or ACh, respectively. Bath application of 10(-6) NPY, a concentration that strongly inhibited the stratum radiatum-CA1 synapse had no effect on CA3 neuron resting potential, input resistance or action potential amplitude, threshold, or duration. NPY also does not alter the amplitude or duration of the prolonged CA3 action potentials evoked in the presence of TTX, tetraethyl-ammonium, and elevated external Ca2+ or those evoked in the presence of TTX and Ba2+ ions. NPY therefore does not alter the passive or active properties of the somata of the presynaptic CA3 neurons. Neither the afferent fiber volley of the Schaffer collaterals in stratum radiatum of area CA1 nor the excitability of the CA3 terminals in CA1 was affected by NPY application. However, application of the transient K+ current blocker, 4-aminopyridine (4-AP) at concentrations of 10 and 50 microM, completely abolished the action of 10(-6) M NPY on the stratum radiatum-CA1 excitatory synaptic potentials. This action of 4-AP could be reversed by reducing extracellular Ca2+ concentrations from a control level of 1.5 to 0.7 mM (in 10 microM 4-AP) and to 0.5 mM (in 50 microM 4-AP). The evidence suggests that NPY inhibits excitatory synaptic transmission at the Schaffer collateral-CA1 synapse by acting directly at the terminal to reduce a Ca2+ influx.

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