Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses to depolarizing current injection were assessed with whole-cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage-gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of spiral ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed.

Learning triggers alterations in gene transcription in brain regions such as the hippocampus and the entorhinal cortex (EC) that are necessary for long-term memory (LTM) formation. Here, we identify an essential role for the G9a/GLP lysine dimethyltransferase complex and the histone H3 lysine 9 di-methylation (H3K9me2) marks it catalyzes, in the transcriptional regulation of genes in area CA1 of the rat hippocampus and the EC during memory consolidation. Contextual fear learning increased global levels of H3K9me2 in area CA1 and the EC, with observable changes at the Zif268, DNMT3a, BDNF exon IV, and cFOS gene promoters, which occurred in concert with mRNA expression. Inhibition of G9a/GLP in the EC, but not in the hippocampus, enhanced contextual fear conditioning relative to control animals. The inhibition of G9a/GLP in the EC induced several histone modifications that include not only methylation but also acetylation. Surprisingly, we found that down-regulation of G9a/GLP activity in the EC enhanced H3K9me2 in area CA1, resulting in transcriptional silencing of the non-memory permissive gene COMT in the hippocampus. In addition, synaptic plasticity studies at two distinct EC-CA1 cellular pathways revealed that G9a/GLP activity is critical for hippocampus-dependent long-term potentiation initiated in the EC via the perforant pathway, but not the temporoammonic pathway. Together, these data demonstrate that G9a/GLP differentially regulates gene transcription in the hippocampus and the EC during memory consolidation. Furthermore, these findings support the possibility of role for G9a/GLP in the regulation of cellular and molecular cross-talk between these two brain regions during LTM formation.

It is now well established that sensory neurons and receptors display characteristic morphological and electrophysiological properties tailored to their functions. This is especially evident in the auditory system, where cells are arranged tonotopically and are highly specialized for precise coding of frequency-and timing-dependent auditory information. Less well understood, however, are the mechanisms that give rise to these biophysical properties. We have provided insight into this issue by using whole-cell current-clamp recordings and immunocytochemistry to show that BDNF and NT-3, neurotrophins found normally in the cochlea, have profound effects on the firing properties and ion channel distribution of spiral ganglion neurons in the murine cochlea. Exposure of neurons to BDNF caused all neurons, regardless of their original cochlear position, to display characteristics of the basal neurons. Conversely, NT-3 caused cells to show the properties of apical neurons. These results are consistent with oppositely oriented gradients of these two neurotrophins and/or their high-affinity receptors along the tonotopic map, and they suggest that a combination of neurotrophins are necessary to establish the characteristic firing features of postnatal spiral ganglion neurons.

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We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation (Mo & Davis, 1997a). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α‐dendrotoxin (α‐DTX) to eliminate the contribution of a class of voltage‐gated K+ channels and assessed its effects on a variety of electrophysiological properties by using the whole‐cell configuration of the patch‐clamp technique. Exposure to α‐DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non‐monotonic relationship between number of action potentials fired and membrane potential in the presence of α‐DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α‐DTX‐sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half‐maximal activation voltages of –63 and 12 mV for the two components. Because α‐DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1‐selective blocker dendrotoxin K (DTX‐K). We found that this antagonist reproduced the effects of α‐DTX on neuronal firing, and that the DTX‐K‐sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage‐activated component of DTX‐sensitive current with a potential contribution from the high voltage‐activated component at more depolarized potentials. In addition, the effects of DTX‐K indicate that Kv1.1 subunits are important constituents of the underlying voltage‐gated potassium channels.