Neuropeptide Y (NPY) Differentially Modulates Excitatory and Inhibitory Synaptic Transmission in Layer V of Rat Neocortex.
Abstract number :
1.028
Submission category :
Year :
2001
Submission ID :
2735
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
A. Bacci, Ph.D., Dept. Neurology, Stanford University, Stanford, CA; J.R. Huguenard, Ph.D., Dept. Neurology, Stanford University, Stanford, CA; D.A. Prince, M.D., Dept. Neurology, Stanford University, Stanford, CA
RATIONALE: Previous studies have shown that NPY has anticonvulsant actions in hippocampus through presynaptic effects that depress excitatory synaptic events, without affecting inhibition (Klapstein and Colmers (1993), Hippocampus 3:103-11). We tested this hypothesis by examining potential effects on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) in rat neocortex.
METHODS: Whole cell recordings were obtained from directly-visualized layer V pyramidal (P) neurons in sensory-motor cortical slices from P13-20 rats. Cells were characterized in current-clamp, and the effects of local NPY perfusions on evoked postsynaptic currents were then assessed in voltage clamp.
RESULTS: The amplitude of evoked monosynaptic IPSCs (eIPSCs) was not affected by a 10 min local perfusion of 1 [mu]M NPY, but a late, robust increase in eIPSC amplitude lasting as long as the longest recordings (up to 80 min) occurred following NPY washout. eIPSCs in control solution had stable amplitudes during similar prolonged recordings. NPY did not affect the frequency or amplitude of mIPSCs recorded in 1 [mu]M TTX. Increases in [K+]o from 2.5 to 20 mM induced a prominent Ca-dependent increase in mIPSC frequency, but not amplitude. Under these conditions NPY produced long-lasting increases in mIPSC frequency. Similar NPY applications resulted in prompt, robust, long-lasting decreases in amplitude of evoked AMPA receptor-mediated EPSCs, recorded from P neurons.
CONCLUSIONS: These data indicate that NPY presynaptically modulates inhibitory synaptic transmission onto P neurons by increasing Ca-dependent release of GABA from presynaptic terminals. On the other hand, NPY decreases glutamatergic excitation on P neurons, as reported in other cortical structures (McQuiston and Colmers (1996) J Neurophysiol. 76:3159-68) This differential modulation of excitation and inhibition by NPY in neocortical pyramidal neurons may be mediated by different receptors and/or different intracellular coupling mechanisms. Like other peptides, NPY is expected to be released during intense neuronal activity, such as that occurring during epilepsy and this, together with the long term actions described here, make it an ideal endogenous antiepileptic neurotransmitter.
Supported by NINDS Grants 06477 and 39579, and the Pimley Research and Training Funds.
Support: NINDS Grants 06477 and 39579, and the Pimley Research and Training Funds.