Scientific Understanding of Consciousness
Dendritic Spikes enhance Stimulus Selectivity
Nature 503, 115–120 (07 November 2013)
Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo
Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Spencer L. Smith, Ikuko T. Smith, Tiago Branco & Michael Häusser
Department of Cell Biology and Physiology and Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Spencer L. Smith & Ikuko T. Smith
Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 0QH, UK
Neuronal dendrites are electrically excitable: they can generate regenerative events such as dendritic spikes in response to sufficiently strong synaptic input. Although such events have been observed in many neuronal types, it is not well understood how active dendrites contribute to the tuning of neuronal output in vivo. Here we show that dendritic spikes increase the selectivity of neuronal responses to the orientation of a visual stimulus (orientation tuning). We performed direct patch-clamp recordings from the dendrites of pyramidal neurons in the primary visual cortex of lightly anaesthetized and awake mice, during sensory processing. Visual stimulation triggered regenerative local dendritic spikes that were distinct from back-propagating action potentials. These events were orientation tuned and were suppressed by either hyperpolarization of membrane potential or intracellular blockade of NMDA (N-methyl-d-aspartate) receptors. Both of these manipulations also decreased the selectivity of subthreshold orientation tuning measured at the soma, thus linking dendritic regenerative events to somatic orientation tuning. Together, our results suggest that dendritic spikes that are triggered by visual input contribute to a fundamental cortical computation: enhancing orientation selectivity in the visual cortex. Thus, dendritic excitability is an essential component of behaviourally relevant computations in neurons.
Neuronal dendrites express voltage-dependent Ca2+ and Na+ channels that confer electrical excitability, particularly the ability to support the active back-propagation of action potentials and the initiation of local dendritic spikes. In addition, the voltage-dependent Mg2+ block of synaptic NMDA receptors can also support nonlinear synaptic integration and dendritic spike initiation. These mechanisms of active synaptic integration have been probed extensively in vitro. Dendritic spikes have also been observed in vivo under certain conditions; however, it remains unclear whether they are involved in behaviourally relevant computations. To investigate whether dendritic non-linearities can contribute to a well-known example of cortical computation, orientation tuning in the visual cortex, we made direct dendritic patch-clamp recordings from layer 2/3 neurons in the mouse visual cortex.
Our experimental results and compartmental modelling suggest that synaptic input causes a dendritic depolarization that activates voltage-dependent ion channels and relieves the Mg2+ block of NMDA receptors. This results in a supralinear, local regenerative event that includes dendritic Na+ spikes. The slow time course of the NMDA receptor current component of the regenerative events causes a prolonged depolarization envelope that propagates to the soma and enhances axonal output. Thus, local computational subunits generated by voltage-dependent mechanisms in dendrites are activated by sensory input in vivo, provide an orientation-tuned signal to the soma and thereby help determine stimulus selectivity.
Dendritic regenerative events provide a mechanism by which a relatively small number of inputs can drive spike output, changing the effective connectivity between local functional groups of neurons or mitigating the noise in cortical circuits, by ensuring that variable synaptic input can result in a more reliable postsynaptic response. Our data from experiments on awake mice demonstrate that these dendritic events occur during alert sensory processing. Because dendrite-targeting inhibitory interneurons are inhibited in awake mice during sensory stimulation, this circuitry might have a key role in gating sensory input. Overall, our results demonstrate that dendrites are not passive integrators of sensory-driven input in vivo. Rather, sensory input engages dendritic voltage-dependent mechanisms and thereby generates local regenerative events and dendritic spikes, which have an important role in shaping orientation selectivity, a quintessential cortical computation.
Return to — Neural Network