Symposium overview and historical perspective: dendrodendritic synapses: past, present, and future

Abstract

Synapses between dendrites are at the core of mechanisms for processing odor stimuli, as well as for processing in many other brain systems. A perspective on the development of our understanding of these mechanisms may therefore be of interest. Studies of the olfactory bulb leading to the discovery of dendrodendritic synapses began in 1959. They involved a multidisciplinary approach that included Golgi cell morphology, electrophysiology, a microcircuit wiring diagram, membrane biophysics, theory of field potentials, cable theory, dendritic electrotonus theory, computational models of mitral and granule cells, prediction by the models of dendrodendritic synaptic interactions, confirmation with electron microscopy using single sections and serial sections, and final integration in the reports of feedback and lateral inhibitory interactions in 1966 and 1968. Following the discovery of glomerular odor maps in the 1970s, the functional significance of the dendrodendritic inhibition in processing the maps has been increasingly documented. Recent experimental and computational studies are revealing how these synapses are organized into distributed systems for processing the odor maps. Future studies need to situate dendrodendritic mechanisms in these distributed systems and correlate them with the tight functional loops between olfactory bulb and olfactory cortex. Studies in awake behaving animals will be increasingly important. The relations of dendritic mechanisms to perception, memory, and the pathogenesis of disorders such as Alzheimer’s will be rich fields for study. Dendrites and their synapses should continue to provide ideal models for the study of basic mechanisms of cortical integration and the neural basis of smell.

Fig. 1

Model of dendrodendritic interactions between mitral and granule cells in the mammalian olfactory bulb, based on experimental evidence and predictions from computational modeling. A. Sequence of time periods I-III is shown after antidromic invasion of mitral cells. In time period I-II, a mitral cell dendrite (open profile) is depolarized (D) by invading action potential from the soma, activating excitatory (E) synapse onto granule cell dendrite (shaded). In time period II-III, the depolarized (D) spine activates an inhibitory (I) synapse back onto the mitral cell dendrite. This action continues into period III. B. Diagram showing how antidromic (AD) invasion of a mitral cell leads to lateral inhibition of a neighboring mitral cell through electrotonic spread of the granule cell depolarization within the granule cell dendritie tree. Orthodromic (OD) activation from the glomeruli through the primary dendrite leads to similar activation of the lateral dendrites and consequent feedback and lateral inhibition. From (6)

Fig. 2

Incorporation of the original dendrodendritic circuit into glomerular units for widely distributed lateral inhibition in the olfactory bulb, based on recent studies (see text). Two glomerular units are shown, each consisting of a glomerulus receiving inputs from its olfactory receptor neuron (ORN) subset (J,K) and connecting to a subset of mitral/tufted (M/T) cells and their interneurons: periglomerular (PG) cells at the glomerular layer, and granule (GR) cells deep to the mitral cell body layer. A backpropagating action potential (bAP) in the left mitral cell lateral dendrite provides full activation of the granule cells within the glomerular unit on the right, independent of distance, to mediate “non-topographical” lateral inhibition in processing the distributed odor maps laid down in the glomeruli by the activated ORNs. Adapted from (33)