Principles of synaptic organization in human cortical networks

The human cerebral cortex is the most sophisticated biological machine we know; it is the seat of higher cognition, memory and thought. The basic architecture and the component cell types of the human neocortex appear similar to other, more widely studied mammalian brains (rodents and primates). However, little is known about synaptic function in humans. Given the critical role of synaptic function in cognition, questions about human synaptic function assume the highest importance. Studying synaptic communication in human neuronal circuits is not possible in situ but can be done using a remarkable resource: tissue that has been resected from the brains of patients having neurosurgical treatment and kept alive in artificial cerebrospinal fluid.

The student will use resected human cortical tissue to examine the structure and function of neuronal synapses, using a range of state-of-the-art imaging, electrophysiology and electron microscopy techniques. Experimental findings will be incorporated into anatomically accurate computational models, to explore how neuronal communication may flow through human cortical networks. The student will examine how neuromodulators such as acetylcholine, dopamine and serotonin, which mediate various cognitive, executive and emotional functions, may alter synaptic communication and dendritic excitability and the propensity towards epileptic discharges. The student will test the hypothesis that the peculiarly long dendrites in human pyramidal cells confer a special facility for compartmentalizing activity and achieving rapid state changes. These functional features may underlie short-term memory and attentional switching but also carry the risk of tipping into epileptic pathological discharging. 

The supervisorial team combines expertise in the anatomy and physiology of mammalian neocortical microcircuits, statistical and computational modelling (Ramaswamy), cellular electrophysiology and imaging techniques and epileptic pathophysiology (Trevelyan & Ramaswamy). Our recent work has revealed the cellular and synaptic organizational principles of cortical networks (Ramaswamy); the principles of seizure initiation and termination (Trevelyan); ionic redistribution that confer variable network functions during circadian cycles (Trevelyan), and the anatomy, physiology and pharmacology of monoaminergic neuromodulator systems and the impact of serotonin on cortical function (Ramaswamy & Trevelyan). 

This timely project, supervised by an internationally recognized team, is an excellent opportunity for a student to be trained in the principles and analytical techniques of experimental and computational neuroscience using resected human brain tissue. 

Funding

PhD studentships are funded by the Reece Foundation for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant and a stipend (Year 1: £22,000, Year 2: £23,000. Year 3: £24,000. Year 4: £25,000). Applications are welcomed from students in all countries, although students from outside the UK will be required to pay full international fees. International students may be eligible for additional financial support to cover some, or all, of these fees.

Enquiries

Dr Srikanth Ramaswamy [Email Address Removed]

Centre for Neuroscience: [Email Address Removed]

Applications

https://www.ncl.ac.uk/research/transformative-neuroscience/studentship/