Developmental profile of localized spontaneous Ca²⁺ release events in the dendrites of rat hippocampal pyramidal neurons

Abstract

Recent experiments demonstrate that localized spontaneous Ca²⁺ release events can be detected in the dendrites of pyramidal cells in the hippocampus and other neurons (J. Neurosci. 29 (2009) 7833–7845). These events have some properties that resemble ryanodine receptor mediated “sparks” in myocytes, and some that resemble IP₃ receptor mediated “puffs” in oocytes. They can be detected in the dendrites of rats of all tested ages between P3 and P80 (with sparser sampling in older rats), suggesting that they serve a general signaling function and are not just important in development. However, in younger rats the amplitudes of the events are larger than the amplitudes in older animals and almost as large as the amplitudes of Ca²⁺ signals from backpropagating action potentials (bAPs). The rise time of the event signal is fast at all ages and is comparable to the rise time of the bAP fluorescence signal at the same dendritic location. The decay time is slower in younger animals, primarily because of weaker Ca²⁺ extrusion mechanisms at that age. Diffusion away from a brief localized source is the major determinant of decay at all ages. A simple computational model closely simulates these events with extrusion rate the only age dependent variable.

Introduction

Calcium concentration ([Ca²⁺]_i) changes regulate physiological processes in all cells. In neurons, with the complex arborization and specializations in both dendrites and axons, it is clear that the location of these changes is critical. Ca²⁺ entry through voltage gated Ca²⁺ channels (VGCCs) in the presynaptic terminals and boutons regulates transmitter release. Ca²⁺ entry through postsynaptic ligand-gated receptors, especially NMDA receptors, regulates the induction of some forms of synaptic plasticity and other physiological processes. Widespread Ca²⁺ entry following backpropagating action potentials (bAPs) also contributes to some forms of plasticity. The role of Ca²⁺ release from internal stores in neurons has been less understood, with little data on the underlying mechanisms, spatial distribution, or functions of these changes under physiological conditions.

One form of Ca²⁺ release in pyramidal neurons results from synaptic activation of metabotropic glutamate receptors (mGluRs). This release occurs either as large amplitude propagating waves [1], [2], [3] or as smaller Ca²⁺ entry near spines [4]. Localized Ca²⁺ release, mediated either by inositol 1,4,5-trisphosphate (IP₃) receptors (“puffs”) or by ryanodine (RyR) receptors (“sparks”) have been described in a variety of preparations including neurons [5], [6], [7], [8]. Two forms of localized Ca²⁺ release have been detected in dendrites. In slice cultures, localized Ca²⁺ release, associated with GABAergic synapses, has been shown to modulate the extension of dendritic processes and may contribute to other aspects of neuronal development [9]. In acute slices recent experiments indicate that faster Ca²⁺ release events occur spontaneously in dendrites [10], presynaptic terminals [11], [12], and cell bodies [11]. Spontaneous Ca²⁺ release events in dendrites occur primarily near branch points and their frequency can be modulated by changes in membrane potential and weak mGluR mediated synaptic trains [10]. The specific functions of these Ca²⁺ release events are not clear.

To help understand the significance of the Ca²⁺ release events in dendrites we examined their properties in CA1 pyramidal neurons from animals of different ages. Most properties were similar but two parameters changed with age. The amplitudes were larger and the decay times were slower in younger animals. The increase in decay time with age was primarily due to the stronger combined effect of plasma membrane, Na/Ca exchange, and SERCA pumps in older animals. The small changes in intrinsic properties with age suggest that these Ca²⁺ release events may have a general signaling role in neurons and are not just important during development.