Olfactory bulb microcircuit

 

This project explored the intrinsic properties of olfactory bulb output neurons. We showed that input from the olfactory nerve activates Ca2+channels located in the primary dendrites and these contribute to dendritic glutamate release. The resulting depolarisation and boosted glutamate release synchronises the activity of multiple output neurons belonging to the same glomerulus. The papers can be found here and here

Potassium channels in the auditory brainstem

A series of projects examined how different voltage-gated K+ channels enable a fast inverting relay neuron in the auditory brainstem to fulfil its specialised role in sound source localisation. Key papers from this work are here and here. The image to the left shows Kv3.1 staining in the MNTB, note the puncta in the axons where the nodes of ranvier are labelled.
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Potassium channel physiology in the MNTB

Rapid mapping of receptive fields

And its application to multi-neuronal electrophysiology and imaging

Neurons in sensory systems have receptive fields. In the somatosensory system, this might be an area of the skin to which the neuron is responsive, whereas in the visual system the receptive field is an area on the retina. Several properties of the receptive field are of interest. The spatial extent of the receptive field, e.g. the area on the retina to which the neuron is responsive, and the temporal characteristics, e.g. when will the neuron respond after applying a stimulus. Measuring the properties of a neuron’s receptive field is an important step towards understanding its function.

 

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The spatiotemporal receptive field of an OFF retinal ganglion cell. The square in the bottom left corner indicates the time of stimulation. Field of view is 900 µm x900 µm. Data is played at 1/20th real time 

 

This project developed a new method that allows the rapid mapping of receptive fields from multiple neurons simultaneously. The procedure is illustrated to the right and the full details are available in the paper hereA series of bars are flashed at different locations across the retina and this is repeated with the bars rotated to cover at least 5 evenly spaced angles. The receptive fields can then be easily recovered using an algorithm applied in CAT scans, the filtered back projection. The code to implement this method is available here.
We showed that the FBP method can recover both the spatial and temporal components of the receptive field. The FBP method had several advantages over the frequently used “spike-triggered average”  approach. The FBP could recover receptive fields significantly faster, with higher signal to noise and the resolution of the temporal impulse response was superior.
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Summary of the method
We also demonstrated how this method is suitable for functional imaging of neural activity. Imaging data is often noisy and clear unitary events such as spikes are not readily discernible. As our method does not rely on detection of events it readily lends itself to mapping receptive fields of neurons measured in imaging experiments. We demonstrated this by mapping the receptive fields of an array of retinal bipolar cell synapses expressing SyGCaMP6 shown below.

Motion Anticipation in the retina

General Features of the retinal connectome determine the computation of motion anticipation

 

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A Retinal Ganglion Cell filled with Alexa 488 to recover its morphology
Light is converted into electrical signals by specialized cells in the retina called photoreceptors. This conversion process, termed phototransduction, is relatively slow, taking around a tenth of a second. Although this might not sound like a long time, it is enough for a tennis ball to have travelled 3-4 meters when served by a professional.
 
Despite this, we do not experience moving objects being delayed, which indicates that moving objects are somehow processed more rapidly. An example of how moving objects are processed differently to static objects can be seen in the flash-lag illusion. This apparent faster processing of moving objects begins in the eye.
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Selective disruption of inhibition in a single retinal ganglion cell
Retinal ganglion cells (pictured), which send signals from the retina to the rest of the brain, respond earlier than expected for moving objects, overcoming the slow process of phototransduction. This phenomenon has been termed “motion anticipation”. This project revealed how motion anticipation arises from the circuitry of the retina.
Using a combination of electrical recordings and computer simulations, we showed that inhibitory signals play a key role in motion anticipation. In particular, we found that an excess of inhibitory inputs onto retinal ganglion cells enables motion anticipation for objects moving in any direction across the retina. 
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Computational model showing the effect of inhibition for a moving stimulus
The project described how the non-linear interaction of excitatory and inhibitory synapses, within ganglion cell dendrites, enables encoding of the actual position of a moving object instead of its delayed representation. The fact that retinal ganglion cells receive an excess of inhibitory inputs is a long-observed feature of retinal wiring, and a role for this can now be understood in terms of providing the mechanism of motion anticipation. The full paper can be read here