Publications (3)9.55 Total impact
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Article: AMPAR-mediated synaptic transmission in the CA1 hippocampal region of neonatal rats: unexpected resistance to repeated ethanol exposure.
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ABSTRACT: Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamatergic receptors (AMPAR) mediate most of the fast excitatory synaptic transmission in mature neurons. In contrast, a number of developing synapses do not express AMPARs; these are gradually acquired in an activity-driven manner during the first week of life in rats, which is equivalent to the third trimester of human pregnancy. Neuronal stimulation has been shown to drive high conductance Ca(2+)-permeable AMPARs into the synapse, strengthening glutamatergic synaptic transmission. Alterations in this process could induce premature stabilization or inappropriate elimination of newly formed synapses and contribute to the hippocampal abnormalities associated with fetal alcohol spectrum disorder. Previous studies from our laboratory performed with hippocampal slices from neonatal rats showed that acute ethanol exposure exerts potent stimulant effects on CA1 and CA3 neuronal networks. However, the impact of these in vitro actions of acute ethanol exposure is unknown. Here, we tested the hypothesis that repeated in vivo exposure to ethanol strengthens AMPAR-mediated neurotransmission in the CA1 region by means of an increase in synaptic expression of Ca(2+)-permeable AMPARs. We exposed rats to ethanol vapor (serum ethanol concentration approximately 40 mM) or air for 4h/day from postnatal day (P) 2-6. In brain slices prepared at P4-6, we found no significant effect of ethanol exposure on input-output curves for AMPAR-mediated field excitatory postsynaptic potentials (fEPSPs), the contribution of Ca(2+)-permeable AMPARs to these fEPSPs, or the acute effect of ethanol on fEPSP amplitude. These results suggest that homeostatic plasticity mechanisms act to maintain glutamatergic synaptic strength and ethanol sensitivity in response to repeated developmental ethanol exposure.Alcohol (Fayetteville, N.Y.) 12/2009; 43(8):619-25. · 2.41 Impact Factor -
Article: Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse.
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ABSTRACT: Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF-LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)-dependent responses in Purkinje cells, both of which are involved in PF-LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF-LTP and that PF-LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF-LTD could contribute to the motor coordination deficits resulting from alcohol consumption.Journal of Neurophysiology 11/2008; 100(6):3167-74. · 3.32 Impact Factor -
Article: Ethanol decreases Purkinje neuron excitability by increasing GABA release in rat cerebellar slices.
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ABSTRACT: Cerebellar Purkinje neurons (PNs) receive inhibitory GABAergic input from stellate and basket cells, which are located in the outer and inner portions of the molecular layer, respectively. Ethanol (EtOH) was recently shown to increase GABAergic transmission at PNs via a mechanism that involves enhanced calcium release from presynaptic internal stores (J Pharmacol Exp Ther 323:356-364, 2007). Here, we further characterized the effect of EtOH on GABA release and assessed its impact on PN excitability. Using whole-cell patch-clamp electrophysiological techniques in cerebellar vermis parasagittal slices, we found that EtOH acutely increases the frequency but not the amplitude or half-width of miniature and spontaneous inhibitory postsynaptic currents (IPSCs). EtOH significantly increased the amplitude and decreased the paired pulse ratio of IPSCs evoked by stimulation in the outer but not inner molecular layer. In current clamp, EtOH decreased both the amplitude of excitatory postsynaptic potentials evoked in PNs by granule cell axon stimulation and the number of action potentials triggered by these events; these effects depended on GABA(A) receptor activation because they were not observed in presence of bicuculline. Loose-patch cell-attached PN recordings revealed that neither the spontaneous action potential firing frequency nor the coefficient of variation of the interspike interval was altered by acute EtOH exposure. These findings suggest that EtOH differentially affects GABAergic transmission at stellate cell- and basket cell-to-PN synapses and that it modulates PN firing triggered by granule cell axonal input. These effects could be in part responsible for the cerebellar impairments associated with acute EtOH intoxication.Journal of Pharmacology and Experimental Therapeutics 09/2008; 327(3):910-7. · 3.83 Impact Factor
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2008
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University of New Mexico
- Department of Neurosciences
Albuquerque, NM, USA
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