Electrical properties of dendrites relevant to dendritic transmitter release

Abstract

The dendritic geometry, the passive membrane properties, and the densities, distribution and kinetics of voltage-gated channels together determine the compartmentalization of electrical signals in dendrites, and how these electrical compartments interact. The degree of spatial restriction of electrical signals in dendrites has direct consequences for the input-output relation of dendritic trees. This is true even if neuronal output is regulated only in the classical manner by the action potential propagating down the axon (Mel, 1993; Koch, 1999; Häusser et al, 2000; Segev and London, 2000; Poirazi et al, 2003; HSusser and Mel, 2003; Polsky et al., 2004; Spruston and Kath, 2004), but the role of electrical compartments in determining the neuronal input-output relation is particularly important when neuronal output is mediated by dendritic release of neurotransmitter (Fig. 5). With transmitter release from its dendrites a neuron acquires the potential for multiple outputs, and a single neuron can thus accommodate the function of an entire network of simple units, transforming multiple inputs into multiple outputs (e.g. Euler et al., 2002; Cuntz et al., 2003). This is in contrast to the classical picture with a single output via the axon (unless there are local failures of action potential propagation in the axon: Debanne, 2004, or the action potential waveform in axonal boutons can be modulated: Geiger and Jonas, 2000). The possibility that the backpropagating action potential can trigger and/or enhance dendritic release of transmitter further emphasizes the importance of the retrograde (soma → dendrite) flow of information, which challenges the classical view originally proposed by Cajal. Beyond the ongoing processing of synaptic inputs, electrical compartmentalization of dendrites also has consequences for long-term synaptic plasticity (Häusser and Mel, 2003; Mehta, 2004). Learning rules based on dendritic spikes (Poirazi and Mel, 2001; Goldberg et al., 2002; Golding et al., 2002; Mehta, 2004) may involve retrograde signalling via dendritic release of transmitters. This has been shown to be the case for the LTD component of spike timing-dependent synaptic plasticity between neocortical layer 5 pyramidal neurons (Sjostrom et al., 2003), which is dependent on endocannabinoid release from the postsynaptic dendrites, triggered by the backpropagating action potential. Hebbian synaptic plasticity is inherently unstable, as it represents a form of positive feedback, this problem is particularly acute when synapses on dendrites are involved (Goldberg et al., 2002; Roth and London, 2004; Rumsey and Abbott, 2004). Various homeostatic plasticity mechanisms (Turrigiano and Nelson, 2004) at different spatial and time scales are probably needed to balance and control the instability due to Hebbian plasticity mechanisms. Homeostatic mechanisms could act via intracellular signalling, particularly via [Ca2+]i as an indicator of neuronal activity (Liu et al., 1998) or via dendritic release and extracellular spread of a transmitter whose concentration is signalled back to the neuron by dendritic autoreceptors. An intriguing possibility is that dendritic release of transmitter could in turn modify the electrical properties of the dendrites and thus alter subsequent release of transmitter. This would represent a form of intrinsic metaplasticity in which dendritic transmitter release could regulate not only itself but also the potential for future synaptic plasticity. A prerequisite for a deeper understanding of the contribution of dendritic transmitter release to information processing and learning in neuronal networks is knowledge of the underlying mechanisms. Which experiments are now required to improve our understanding of the link between dendritic excitability and dendritic release? First, we need a more complete characterization of electrical properties of dendrites in neurons exhibiting dendritic release, including the properties and distribution of dendritic voltagegated ion channels. In only a few model systems, such as mitral cells of the olfactory bulb (chapter 7, this volume), have the electrical properties of dendrites been investigated in detail. Second, a more quantitative understanding of how electrical signals are translated into dendritic Ca2+ signals is required, including a complete description of dendritic Ca2+ dynamics (Markram et al., 1998). Finally, our understanding of the voltage- and/or Ca2+ dependence of dendritic transmitter release and the underlying biophysical mechanisms still lags far behind our understanding of transmitter release at axonal boutons. Together, this information will allow a deeper understanding of how electrical signals in dendrites are translated into dendritic release of transmitters, and provide us with a set of molecular targets which will enable us to better define the role of dendritic transmitter release in relation to behaviour.