Donna L. Gruol

Ca²⁺ signaling is important in many fundamental neuronal processes including neurotransmission, synaptic plasticity, neuronal development, and gene expression. In cerebellar Purkinje neurons, Ca²⁺ signaling has been studied primarily in the dendritic region where increases in local Ca²⁺ have been shown to occur with both synaptic events and spontaneous electrical activity involving P-type voltage-gated Ca²⁺ channels (VGCCs), the predominant VGCC expressed by Purkinje neurons. Here we show that Ca²⁺ signaling is also a prominent feature of immature Purkinje neurons at developmental stages that precede expression of dendritic structure and involves L-type rather than P-type VGCCs. Immature Purkinje neurons acutely dissociated from postnatal day 4–7 rat pups exhibit spontaneous cytoplasmic Ca²⁺ oscillations. The Ca²⁺oscillations require entry of extracellular Ca²⁺, are blocked by tetrodotoxin, are communicated to the nucleus, and correlate closely with patterns of endogenously generated spontaneous and evoked electrical activity recorded in the neurons. Immunocytochemistry showed that L-, N-, and P/Q-types of VGCCs are present on the somata of the Purkinje neurons at this age. However, only the L-type VGCC antagonist nimodipine effectively antagonized the Ca²⁺ oscillations; inhibitors of P/Q and N-type VGCCs were relatively ineffective. Release of Ca²⁺from intracellular Ca²⁺ stores significantly amplified the Ca²⁺ signals of external origin. These results show that a somatic signaling pathway that generates intracellular Ca²⁺ oscillations and involves L-type VGCCs and intracellular Ca²⁺ stores plays a prominent role in the Ca²⁺ dynamics of early developing Purkinje neurons and may play an important role in communicating developmental cues to the nucleus.

Tetrodotoxin

10.1523/jneurosci.20-19-07394.2000

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Citations (72)

Neuroadaptive changes in cerebellar neurons induced by chronic exposure to IL-6

Journal of Neuroimmunology (2011)

Donna L. Gruol A. Puro Christine Hao Pennelope Blakely E. Janneke

Pathophysiology

10.1016/j.jneuroim.2011.08.009

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Citations (13)

Altered hippocampal synaptic transmission in transgenic mice with astrocyte-targeted enhanced CCL2 expression