Skip to main content
Neil Hardingham

Dr Neil Hardingham

(he/him)

Lecturer

School of Biosciences

Overview

I am interested in synaptic transmission and also in neuronal morphology and circuitry in the cerebral cortex. The cortex plays a key role in processing of sensory inputs and also much higher level functions like decision making and executive control. Understanding these processes and how they are adjusted by development or synaptic plasticity may help us develop treatments for neurological disorders where neuronal morphology, synaptic transmission and synaptic plasticity are compromised.

Publication

2023

2022

2021

2018

2017

2015

2013

2012

2011

2010

2008

2007

2006

2005

2003

1998

Articles

Websites

Research

Hardingham Research Interests

The cerebral cortex carries out many of the more complex functions of the brain, especially in higher primates; therefore if we are to understand how the brain works we need to understand the cortex. Cortical development is increasingly being linked to neurological disorders such as Schizophrenia, Fragile X syndrome, Mental Retardation and Alzheimer's disease and structural and functional deficits in the cortex are now being linked with these psychological disorders. We need to understand these disorders in order to provide future treatments. Mouse models of neurological conditions have started to help unravel the biological basis of these conditions by showing deficits either in synaptic currents, dendritic arborizations, spine density or neuronal connectivity. Research in the Fox lab where I have worked in Cardiff has shown that disruption of DISC-1 signalling at P7, after cell migration is complete produces deficits in plasticity in mature cortex, but induction of mutant DISC-1 at P28 has no effect (Greenhill et al, Science, 2015). My research has been looking at normal development over this period (P7-P28) and how it is affected by DISC1 disruption and has shown that dendritic development is significantly attenuated over this critical period when compared to wild types (Greenhill et al 2015). Furthermore, properties of synaptic maturation are also attenuated when compared to wild types and spine density is affected on particular orders of dendrites. I have developed robust methodology to be able to investigate both synaptic properties of neurons and also measure neuronal morphology at the dendritic level to measure its' development and also to measure spine density and spine morphology in detail and correlate this with function (Greenhill et al 2015). In addition, I have obtained a constitutive DISC1 mutant (Der1) which accurately replicates the original translocation and am investigating deficits in this mouse, comparing the effects of chronic to transient DISC1 disruption.

Future Research Proposals

Many, if not all neuropsychiatric disorders have cognitive deficits consistent with involvement of the prefrontal cortex, which is involved in many high order cognitive functions, so this is where I am now focussing my attention. I am working on a  DISC1 mutant (the Der-1) which is the first which accurately mimics the original translocation observed in humans which was a high potency risk factor for several neuropsychiatric disorders including schizophrenia. I have already found deficits in prefrontal neurons at both the dendrite and at the spine level, but interestingly the deficits are dendrite specific, with deficits specific to basal dendrites. I would like to extend my research to other mouse models of neurological disorders and hopefully identify commonalities between disease mechanisms.

Schizophrenia has long been proposed to be caused by deficits in connectivity between different brain regions while the prefrontal cortex receives inputs from many different areas of the brain including hippocampus, amygdala and the thalamus. Using optogenetic approaches I am able to stimulate and characterise individual inputs to the prefrontal cortex and map input sites on specific dendritic trees and determine whether various inputs are differently located on dendrites and also whether they are altered in the mutant mice dependant on their location. These experiments could be then followed up by behavioural tests specific to the inputs most affected in the mutants.

Teaching

I teach in a range of neuroscience areas, both lecturing and practical based learning and am interested in implementing a range of learning techniques to further engage students in the learning activities and get them contributing. I have a fellowship in Higher Education at Cardff University (FHEA).

I am involved in organisation of modules at many levels, I am assessment lead (BI2432), examination lead (BI1002) and second year examination liaison officer. I run a week long practical and also run an extended 3 week masters practical.

Contact Details

Email HardinghamNR@cardiff.ac.uk
Telephone +44 29208 76276
Campuses Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX

External profiles