There are a number of potential PhD projects available in the lab, all investigating how neural circuits process visual information. Two example projects are described in more detail below, one using zebrafish and the other mice. If you are interested in these, or other possible projects, please contact Leon at firstname.lastname@example.org.
Project 1: Plasticity of visual processing in the retina
Background: Our work exploits the fact that the retina provides an excellent context in which to study how neural circuits process information: we can control the input to the circuit (light) while observing the activity of neurons and synapses within it. We do this by using multiphoton microscopy to image the activity of fluorescent reporter proteins expressed in live zebrafish. This approach has allowed us to analyse how excitatory and inhibitory neurons within the retinal network and the brain contribute to basic computations underlying vision, such as the detection of motion or the orientation of a spatial feature.
Aims: We will investigate the plasticity of the retinal circuit – changes in the way that visual stimuli are processed according to the recent history of activity. Changes in the properties of synapses within the retina play a key role in such “network adaptation” and these changes can in turn be caused by the release of neuromodulators such as dopamine, somatostatin or Substance P. We will ask how these substances modify the synaptic transmission of the visual signal through the retinal network and how they alter the signals that the retina transmits back to the brain.
Ben James, Lea Darnet, Jose Moya-Diaz, Sofie-Helene Seibel and Leon Lagnado (2018). An amplitude code increases the efficiency of information transmission across a visual synapse.
Jamie Johnston, Sofie-Helene Seibel, Lea Darnet, Sabine Renninger, Michael Orger and Leon Lagnado (2018). A retinal circuit generating a dynamic predictive code for orientated features
Rosa JM, Ruehle S, Ding H, Lagnado L. (2016). Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina. Neuron, 90(2):308-19.
Lagnado, L. & Schmitz, F. (2015). Ribbon synapses and visual processing in the retina. Annual Reviews of Vision Science, 1:235-262.
Esposti, F., Johnston, J., Rosa, J., Leung, K-M., and Lagnado, L. (2013). Olfactory stimulation selectively modulates the OFF pathway in the zebrafish retina. Neuron, 79:97-110.
Nikolaev, A., B. Odermatt, Leung, K.-M. and L. Lagnado. (2013). Synaptic mechanisms of adaptation and sensitization in the retina. Nature Neuroscience, 7:934-4171.
Project 2: Plasticity of visual processing in primary visual cortex
Background: The responses of pyramidal neurons in primary visual cortex (V1) of mice are altered under different behavioural states. For instance, multiphoton imaging of neural calcium reporters (GCaMPs) has shown that a visual stimulus activates pyramidal neurons more strongly when the mouse is locomoting or when it is aroused. This modification of the flow of excitatory signals within VI is caused by interactions between pyramidal neurons and a diverse population of inhibitory (GABAergic) interneuron. Reciprocal interactions between different sub-types of interneurons have been shown to modulate activity in the visual, auditory, somatosensory and prefrontal cortices, and is gated by different behavioural states reflecting attention and arousal.
Aims: We will investigate how interneurons modulate responses in primary visual cortex (V1) of mice under different behavioural states and during the learning of a visual task. Learning of a visual task alters the relation between the activity of two particular subtype of interneuron – the VIPs and SSTs – that are reciprocally connected. We will investigate the possibility that in the VIP-SST circuit, one population of interneurons can dominate over the other depending on the stimulus presented and that the strength of these reciprocal connections is modulated during learning. This project will involve multiphoton imaging of neural and synaptic activity in the visual cortex of awake mice as they learn a visual task.