Research

Synaptic computation in the visual system

We use larval zebrafish to investigate the mechanisms by which neural circuits process visual information, with a special emphasis on the role of synapses as computational elements within these networks. We would like to better understand the principles governing how the visual system extracts meaningful features from sensory inputs, such as contrast or motion, while also adapting to changes in the visual environment or internal state of the animal. By focusing on the retina and higher visual centers, we seek to bridge the gap between synaptic events transmitting visual signals and behavioural outcomes.

Synapses are fundamental components of all neural circuits, regulating the flow and timing of signals carrying information. We are interested in the biophysical basis of synaptic transmission, including the kinetics of vesicle release. For instance, our studies have revealed how ribbon synapses in retinal bipolar cells employ multivesicular release to enhance the efficiency of information transfer.  We also examine how synaptic properties shape the initial stages of visual signal processing in the retina. Retinal bipolar cells, which transmit signals from photoreceptors to ganglion cells, exhibit diverse response properties that adjust with adaptation.

The plasticity of synapses is one of the mechanisms that generates adaptation in the retinal network as a whole, causing it to adjust its input-output relation to prioritize relevant information. Neuromodulators play a pivotal role in reconfiguring synaptic function and signal flow within visual circuits. Dopamine, for example, alters release probabilities at ribbon synapses, shifting the balance between different synaptic coding strategies. Diurnal rhythms that adjust visally-driven behaviours act through such neuromodultors to adjust the efficiency of informtion transmission at these synapses, with higher information rates during the day when visual demands are greatest.

We also investigate how changes in behavioral state, such as those associated with the diurnal cycle, alter early sensory processing. In the retina, this involves inhibitory pathways mediated by amacrine cells that modulate synaptic gain aswell as noise in the retinal circuit. We have investigated how these inhibitory networks contrbute to temporal processing of visual signals, allowing the retina to anticipate motion, suppressing responses to predictable stimuli while enhancing novelty detection.

Our experimental toolkit leverages state-of-the-art optical and genetic methods to interrogate these processes in vivo. We employ fluorescent reporters like iGluSnFR for glutamate release and SyGCaMP for synaptic calcium dynamics, imaged via multiphoton microscopy to capture activity across entire circuits with millisecond precision. Optogenetics allows targeted manipulation of neuron subtypes, testing causal roles in computations. Circuit properties are related to behavioural assays, often carried out simultaneously. Computational approaches play a key role in exploring and understanding our experimetal observations.

The larval zebrafish serves as an unparalleled model for these studies due to its optical transparency, permitting non-invasive imaging of the entire nervous system in intact animals. Genetic tractability facilitates rapid creation of transgenic lines expressing our tools, accelerating hypothesis testing. Developmentally, functional circuits form within days, enabling early investigations of synaptogenesis and plasticity. The ability to correlate brain-wide activity with natural behaviors, like the optomotor response, bridges neural mechanisms to ecology.

To illustrate, our recent work quantifies the link between retinal performance and behavioral reflexes, using iGluSnFR to track individual vesicle releases during motion stimuli, revealing diurnal variations in synaptic efficiency that directly impact the optomotor response (see right).  You can find out more about our research by looking at some of our recent publications or by contacting us.  We’d be more than happy to tell you more!