Project 1: Regulating the short-term dynamics of cortical synapses
Synaptic connections change their efficacy over time. The size and reliability of synaptic responses change from moment to moment depending on recent activity, in a phenomenon known as short-term synaptic plasticity (STP). Each type of synapse has particular properties that determine its STP, generating a tendency to facilitate (strengthen) or depress (weaken) under different patterns of stimulation. Although each type has a characteristic average STP, individual synapses can vary considerably around the average behaviour, with profound implications for the transmission and filtering of information across synaptic pathways. For example, we recently found that STP is strikingly diverse across synapses within the main “thalamocortical” pathway delivering sensory information from the whisker system to the cerebral cortex. However, STP diversity within synaptic populations in the cortex remains poorly understood. Is STP specifically regulated on a cell-by-cell or even synapse-by-synapse level? How might this regulation be achieved?
This project will use electrophysiology and imaging techniques to look at how STP varies from synapse to synapse within a specific cortical pathway crucial to sensory perception. We will examine how different synapses within this single population regulate their dynamic properties and transfer information, and determine whether distinct subtypes of STP behaviour can be found.
The work would suit students with a strong background in biology or the physical sciences. The project will involve testing and applying some exciting new genetically-expressed sensors for optically monitoring synaptic activity, combined with techniques for electrophysiological intracellular recording in brain slices.
Relevant publications:
Maravall M, Diamond ME. Algorithms of whisker-mediated touch perception. Curr Opin Neurobiol 2014; 25: 176-186.
Díaz-Quesada M, Martini FJ, Ferrati G, Bureau I, Maravall M. Diverse thalamocortical short-term plasticity elicited by ongoing stimulation. J Neurosci 2014; 34: 515-526.
Project 2: Neuronal activity underlying sequence recognition
Making sense of the world requires the capacity to recognise patterns that unfold over time. Distinguishing sequential temporal patterns is central to behaviour - for example, for recognising a passage of speech or a melody. Temporal patterning over hundreds of ms or more is a ubiquitous stimulus feature that the brain is particularly good at deciphering and remembering. Yet despite the importance of sequence selectivity, surprisingly little is known about its substrates in the brain. How a sequence is reflected in spiking activity across populations of neurons, integrated over time, and classified as a meaningful entity is elusive.
My lab is beginning an ambitious project aimed at determining how representations of sensory sequences emerge from the activity of populations of neurons in the cerebral cortex. We use a novel sequence recognition task performed by mice to determine sensory input, behavioural output and neuronal responses under controlled conditions. Mice learn to detect arbitrary sequences of stimulation delivered to their whiskers - tactile "songs" or "words". Using in vivo electrophysiology and imaging techniques, we can extract neuronal activity correlated with performance on the task, and measure the effects on behaviour of perturbing this activity. Several questions related to this overall programme would be suitable for a PhD. What are the limits of animals’ performance on the task? How do sequence representations change from stage to stage? Can we design novel analyses to resolve the participation of particular neurons in the task?
This work would suit students with a range of backgrounds, including biology, biological or experimental psychology, or a quantitative subject (mathematics, physics, engineering). Students will need a strong quantitative background or a keen interest in learning quantitative approaches for sensory, systems and behavioural neuroscience. The project will involve a flexible blend of experimental and computational techniques depending on the student’s interests.
Relevant publications:
Maravall M, Diamond ME. Algorithms of whisker-mediated touch perception. Curr Opin Neurobiol 2014; 25: 176-186.
Safaai H, von Heimendahl M, Sorando JM, Diamond ME, Maravall M. Coordinated population activity underlying texture discrimination in rat barrel cortex. J Neurosci 2013; 33: 5843-5855.
Alenda A, Molano-Mazón M, Panzeri S, Maravall M. Sensory input drives multiple intracellular information streams in somatosensory cortex. J Neurosci 2010; 30: 10872-10884.
Lundstrom BN, Fairhall AL, Maravall M. Multiple timescale encoding of slowly varying whisker stimulus envelope in cortical and thalamic neurons in vivo. J Neurosci 2010; 30: 5071-5077.
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