Neuronal activity is a dynamic interplay of the excitatory and inhibitory synaptic input. Persistent changes in synaptic efficacy are thought to be the mechanism underlying learning and memory. Conventionally, astrocytes have not been implicated in these processes, but were regarded as supporting elements. However, recent studies in mixed cell cultures have suggested that astrocytes increase neuronal Ca2+ concentrations and thereby might have the potential to modulate neuronal activity. This proposal will examine the interactions between astrocytes and neurons in hippocampal slices. Preliminary work indicated that interneuronal activity triggers Ca2+ elevations in surrounding astrocytes. In turn, these astrocytes release glutamate that activates N-methyl-D-aspartate (NMDA) receptors and triggers a continuing increase in both the amplitude and frequency of miniature inhibitory postsynaptic currents (mIPSCs) in neighboring CA1 pyramidal neurons. Thus, astrocytic Ca2+ signalling enhances the efficacy of inhibitory input. Astrocytes can be discerned from interneurons or pyramidal neurons in hippocampal slices by using a differential interference contrast (DIC) microscopy technique developed in my laboratory. Therefore, Ca2+ signals can be recorded from DIC-identified astrocytes in slices loaded with fluorescent calcium indicators concurrent with patch-clamp recordings from neighboring pyramidal neurons and/or interneurons. Experimental questions will include: 1. Does interneuronal activity induce astrocytic Ca2+ signaling? 2. Does astrocytic Ca2+ signalling enhance the efficacy of inhibitory input to CA1 pyramidal neurons? What are the mechanisms underlying the induction and expression of long-term potentiation (LTP) of mIPSCs? 3. What are the physiological and pathological functions of long-term potentiation of inhibitory synapses in local hippocampal circuits? This research will increase our understanding of inhibitory synaptic plasticity and potentially provide a target for a new generation of anticonvulsants.
| Kang, Ning; Xu, Jun; Xu, Qiwu et al. (2005) Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. J Neurophysiol 94:4121-30 |
| Kang, Ning; Jiang, Li; He, Wei et al. (2004) Presynaptic inactivation of action potentials and postsynaptic inhibition of GABAA currents contribute to KA-induced disinhibition in CA1 pyramidal neurons. J Neurophysiol 92:873-82 |
| Jiang, L; Xu, J; Nedergaard, M et al. (2001) A kainate receptor increases the efficacy of GABAergic synapses. Neuron 30:503-13 |
| Jiang, L; Sun, S; Nedergaard, M et al. (2000) Paired-pulse modulation at individual GABAergic synapses in rat hippocampus. J Physiol 523 Pt 2:425-39 |
| Kang, J; Jiang, L; Goldman, S A et al. (1998) Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat Neurosci 1:683-92 |
