Mechanisms of Lateral Inhibition in the Olfactory Bulb: Efficiency and Modulation of Spike-Evoked Calcium Influx into Granule Cells

Abstract

Granule cells are axonless local interneurons that mediate lateral inhibitory interactions between the principal neurons of the olfactory bulb via dendrodendritic reciprocal synapses. This unusual arrangement may give rise to functional properties different from conventional lateral inhibition. Although granule cells spike, little is known about the role of the action potential with respect to their synaptic output. To investigate the signals that underlie dendritic release in these cells, two-photon microscopy in rat brain slices was used to image calcium transients in granule cell dendrites and spines. Action potentials evoked calcium transients throughout the dendrites, with amplitudes increasing with distance from soma and attaining a plateau level within the external plexiform layer, the zone of granule cell synaptic output. Transient amplitudes were, on average, equal in size in spines and adjacent dendrites. Surprisingly, both spine and dendritic amplitudes were strongly dependent on membrane potential, decreasing with depolarization and increasing with hyperpolarization from rest. Both the current-voltage relationship and the time course of inactivation were consistent with the known properties of T-type calcium channels, and the voltage dependence was blocked by application of the T-type calcium channel antagonists Ni2+ and mibefradil. In addition, mibefradil reduced action potential-mediated synaptic transmission from granule to mitral cells. The implication of a transiently inactivating calcium channel in synaptic release from granule cells suggests novel mechanisms for the regulation of lateral inhibition in the olfactory bulb.

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

“…In contrast to observations in CA1 pyramidal neurons (Spruston et al 1995) and neocortical layer 2/3 pyramidal neurons (Svoboda et al 1999), these amplitudes do not decrease, but they do increase with distance from the soma and attain a plateau level within the EPL, where the reciprocal spines are located (Egger et al 2003). The decay of dendritic calcium transients is slow (τ = 780 msec).…”

“…The decay of dendritic calcium transients is slow (τ = 780 msec). The dendritic calcium transients require Na + -dependent action potentials and are strongly dependent on the membrane potential, decreasing with depolarization and increasing with hyperpolarization from rest, which is consistent with the properties of T-type calcium channels (Egger et al 2003). T-type calcium channels are known to be expressed in GCs of the AOB (Yunker et al 2003).…”

“…In GCs of the rat MOB, action potentials evoke robust dendritic calcium transients (Egger et al 2003). In contrast to observations in CA1 pyramidal neurons (Spruston et al 1995) and neocortical layer 2/3 pyramidal neurons (Svoboda et al 1999), these amplitudes do not decrease, but they do increase with distance from the soma and attain a plateau level within the EPL, where the reciprocal spines are located (Egger et al 2003).…”

T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

“…They control the response to graded depolarizations in rod bipolar neurons [51,60], are involved in neurotransmitter release in dendrodendritic reciprocal synapses between granule cells (GCs) and mitral/tuftet cells of olfactory bulbs [20,21], control spike-mediated and graded synaptic transmission between oscillatory heart interneurons of leech [34], and regulate the frequency of spontaneous excitatory postsynaptic currents (mEPSCs) in nociceptive neurons [3]. Looking closely at these reports, it appears evident that T-type channels play a role in those neurons that either use graded potentials for signal transmission or display Ca 2+ signals at the synaptic terminals in dendrites and spines that are strongly dependent on the holding membrane potential.…”

“…As shown by several groups, the distal spines of GCs possess presynaptic (transmitter-releasing) and postsynaptic (transmitter-receiving) elements. These terminals express sufficient densities of T-type channels to modulate transmitter release [20]. The presence of T-type channels is evident by two-photon Ca 2+ imaging measurements showing that Ca 2+ transients at the spines and adjacent dendrites of GCs are strongly dependent on membrane potential: decreasing their size with depolarization and increasing with hyperpolarization.…”