Postsynaptic processing mechanisms in the dorsal cochlear nucleus

Voltage-gated Ca{dollar}sp{lcub}2+{rcub}{dollar} conductances (VGCCs) and metabotropic glutamate receptors (mGluRs) are involved in the modulation of synaptic responses throughout the central nervous system. The properties of VGCCs and mGluRs were investigated to ascertain their involvement in the processing of synaptic inputs within the dorsal cochlear nucleus (DCN), a portion of the brainstem complex that is the first central synapse for ascending auditory information.; Whole-cell voltage clamp recordings obtained during pharmacologic blockade of voltage-gated Na{dollar}sp+{dollar} and K{dollar}sp+{dollar} conductances show that the majority of neurons acutely isolated from guinea pig DCN possess a variety of VGCCs. A model incorporating the kinetic properties obtained experimentally demonstrated that VGCCs are capable of producing a large Ca{dollar}sp{lcub}2+{rcub}{dollar} influx in response to action potentials (APs). The spatial distribution of VGCCs within individual neurons was then investigated with the fluorescence imaging of Ca{dollar}sp{lcub}2+{rcub}{dollar} indicators during whole-cell recordings from rat pup DCN slices. These imaging studies revealed that DCN pyramidal and cartwheel cells possess dendritic VGCCs, and a VGCC-mediated dendritic Ca{dollar}sp{lcub}2+{rcub}{dollar} influx can be elicited by the retrograde propagation of somatic APs or AP bursts into the dendritic arbor. Therefore, VGCCs may be involved in the communication of ongoing cellular activity to distal synapses, producing depolarization and Ca{dollar}sp{lcub}2+{rcub}{dollar} influx in response to somatic events at or near synapses.; The effects of mGluR activation on synaptic responses were investigated during recordings of parallel fiber (PF)-evoked responses in a guinea pig DCN slice preparation. Pharmacologic activation of group I mGluRs reversibly depresses PF-evoked field responses obtained during extracellular recordings from the DCN. Subsequent intracellular sharp electrode recordings demonstrated that this depression occurs exclusively at cartwheel cell/PF synapses: the application of mGluR agonists attenuates PF-evoked responses in cartwheel cells, but not PF-evoked responses in pyramidal cells. In addition to the modulation of PF-evoked responses in cartwheel cells, mGluR activation reversibly depolarizes both cartwheel and pyramidal cells, suggesting that functional mGluRs are present in pyramidal cells, but not at PF synapses. Therefore, mGluRs are capable of modulating synaptic responses at glutamatergic synapses in DCN neurons, and may play a role in modulating the communication of ongoing cellular activity to distal synapses.