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Sensory-evoked synaptic integration in cerebellar and cerebral cortical neurons

Key Points

  • Most sensory-evoked synaptic activity occurs at subthreshold levels and rarely results in action potential firing. As such, it can only be measured via intracellular electrophysiology and fast cellular imaging.

  • Integration of a handful of synaptic inputs via temporal summation or the coincident activation of multimodal inputs is necessary to drive action potential output in cerebellar granule cells.

  • Subthreshold receptive fields in the neocortex are exceptionally broad, but through the iceberg effect, only trigger action potential firing in a small region of the receptive field. Broad somatic subthreshold receptive fields result from heterogeneously tuned populations of synapses that are distributed across the dendritic tree.

  • Short-term plasticity can markedly alter synaptic representations of sensory stimuli. However, under certain conditions — for example, receipt of velocity signals in cerebellum and whisker movement signals in the neocortex — synaptic activity exhibits little or no short-term dynamics.

  • Sensory stimulation activates excitatory and inhibitory synapses in concert. This restricts action potential firing to narrow windows of opportunity and reduces output correlations among highly interconnected networks.

  • The accurate measurement of excitatory and inhibitory synaptic conductances in vivo via somatic voltage clamp is prohibited by poor space clamp and the dendritic location of most synapses.

  • Active dendritic conductances further contribute to the difficulty in measuring synaptic conductances and can profoundly alter the properties of sensory-evoked synaptic inputs. The contribution of active conductances may be particularly prominent in behaviourally relevant scenarios, such as active sensation.

Abstract

Neurons integrate synaptic inputs across time and space, a process that determines the transformation of input signals into action potential output. This article explores how synaptic integration contributes to the richness of sensory signalling in the cerebellar and cerebral cortices. Whether a neuron receives a few or a few thousand discrete inputs, most evoked synaptic activity generates only subthreshold membrane potential fluctuations. Sensory tuning of synaptic inputs is typically broad, but short-term dynamics and the interplay between excitation and inhibition restrict action potential firing to narrow windows of opportunity. We highlight the challenges and limitations of the use of somatic recordings in the study of synaptic integration and the importance of active dendritic mechanisms in sensory processing.

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Figure 1: Sensory integration and stimulus reconstruction in simple cells.
Figure 2: Organization and integration of sensory inputs in pyramidal cells.
Figure 3: Short-term synaptic dynamics tune and sharpen receptive fields.
Figure 4: Sensory responses result from co-activation of temporally offset excitatory and inhibitory inputs.
Figure 5: Active dendritic conductances in pyramidal cells of awake behaving animals.

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Acknowledgements

The authors thank S. Chen for feedback on an earlier version of the manuscript. P.C. is supported a UK Medical Research Council (MRC) Career Development Award (G1000512) and a Human Frontier Science Program Young Investigator Award. A.T.S. is supported by the UK MRC (MC_UP_1202/5). S.R.W. is supported by the Australian Research Council (FT100100502) and the NHMRC (APP1004575). T.W.M. is a Wellcome Trust Investigator and is supported by the UK MRC (MC_U1175975156).

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Glossary

Postsynaptic potential

(PSP). A fluctuation in the membrane potential owing to the binding of excitatory transmitter molecules (glutamate) and/or inhibitory transmitter molecules (glycine and GABA) that are released from axon terminals following a presynaptic action potential.

Excitatory postsynaptic currents

Synaptic currents that may be pharmacologically isolated from inhibitory currents recorded in voltage clamp mode and result from the activation of fast glutamatergic receptors.

Horizontal semicircular canals

Fluid-filled tubes that are located in the vestibular organ of the inner ear. Relative movement of fluid within one of the canals corresponds to rotation of the head around the vertical axis.

Stimulus reconstruction

This term describes approaches to calculate approximations of the sensory stimulus based on recorded trains of action potentials or synaptic currents. These can be filters applied to the measured data or Bayesian approaches that determine the most likely stimulus given an observed spike or synaptic current train. These methods help to determine the features in the neuronal data that encode most of the information about the stimulus.

Velocity encoder

A descriptor of a neuron whose synaptic responses most accurately represent velocity rather than acceleration of position of the head during whole-body rotation.

Synaptic receptive fields

The regions of stimulus space in which the presence of a stimulus elicits and/or modulates synaptic activity.

Broadly tuned

Responsiveness to a wide range of stimuli.

Sensory-evoked calcium signals

Changes in calcium levels in dendrites and spines can be measured using fluorescent calcium indicators and serve as a proxy for local electrical activity triggered by a stimulus.

Dendritic conductances

Channel-mediated ion flow in dendrites that can boost or attenuate signal propagation.

Orientation domains

In the visual cortex — for example, of cats — orientation preference varies gradually across the cortical surface, resulting in local regions ('domains') in which neurons with a similar orientation preference are grouped together.

Hypersynchronous network activity

The state of (often unnaturally) high synchrony between large populations of neurons, particularly in epileptic discharges, during which extensive groups of neurons simultaneously fire action potentials within a few milliseconds.

Electrotonically

The term refers to the voltage spread (largely voltage attenuation) along branched structures such as dendrites that is mediated by the 'passive' cellular properties: membrane resistance, membrane capacitance and axial resistance. It can be quantitatively described using cable theory.

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Chadderton, P., Schaefer, A., Williams, S. et al. Sensory-evoked synaptic integration in cerebellar and cerebral cortical neurons. Nat Rev Neurosci 15, 71–83 (2014). https://doi.org/10.1038/nrn3648

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