GABAergic inhibitory interneurons comprise a population of hippocampal cells whose high degree of anatomical and functional divergence make them suitable candidates for controlling the activity of large populations of principal neurons. GABAergic inhibitory interneurons play a major role in the synchronization of neuronal activity and are involved in the generation of large-scale network oscillations. Thus interneurons function as a clock; that dictates when principal cells fire during suprathreshold excitatory drive. Interneurons receive strong excitatory glutamatergic innervation via numerous anatomically distinct afferent projections and recent evidence has demonstrated that the molecular composition of both the AMPA-preferring class of glutamate receptors expressed at interneuron synapses are often distinct from those found at principal cell synapses. Furthermore, single inhibitory interneurons can synthesize distinct AMPA receptors with defined subunit composition and target them to synaptic domains innervated by different afferent inputs. Over the last year Dr McBains lab has investigated differential mechanisms of synaptic transmission onto hippocampal inhibitory interneurons and the role of intrinsic voltage-gated channels in regulating interneuron excitability using high-resolution whole-cell patch clamp recording techniques in brain slices of hippocampus, and auditory and barrel cortex. Specifically, we have demonstrated differential mechanisms of quantal synaptic transmission and estimated the true conductance lifetime for a variety of excitatory synaptic connections onto interneurons. Mechanisms of short and long-term plasticity, frequency dependent transmission, regulation of transmission by presynaptic metabotropic glutamate receptors and an interaction between short and long term changes in transmission at mossy fiber-interneuron and -pyramidal cell targets have also been studied. We have also described two novel forms of interneuron-long term depression of excitatory synaptic transmission between dentate gyrus granule cells and interneurons of the stratum lucidum that require calcium permeation through either Ca-permeable AMPA receptors or NMDA receptors for their induction. Moreover evidence is now emerging that suggests that the mossy fiber-CA3 system engages their interneuron targets via two parallel systems that differentially utilize NMDA receptors to endow distinct firing characteristics on their postsynaptic targets. Differential mechanisms of synaptic transmission between connected pairs of pyramidal neurons of the auditory and barrel cortex was also studied. Connections between pairs of pyramidal neurons in auditory cortex possess two modes of synaptic transmission that make them highly specialized for the processing of transient versus sustained auditory signals. Similar synaptic properties are completely absent from equivalent connections in barrel cortex, another sensory cortical area underscoring the specialized nature of transmission at auditory cortex synapses. Modulation of gamma-frequency oscillations by muscarinic receptor activation in both wildtype and selective muscarine receptor knockouts was also studied. Muscarinic M1 receptor activation is linked to the modulation of two non-selective cation currents in pyramidal neurons that provide a depolarizing bias and increase in action potential firing frequency; two mechanisms identified as being necessary for gamma frequency oscillation induction.
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