Prof Mala Shah
Professor of Neuroscience
UCL School of Pharmacy
- Joined UCL
- 1st Jan 2012
The cortex and hippocampus are two key brain areas that play critical roles in normal functions such as learning and memory as well as disorders such as epilepsy. Our research interests lie in understanding how neurons within these brain areas process information and thereby influences neural network activity. We are particularly interested in determining how voltage-gated ion channels regulate neuronal intrinsic excitability and synaptic transmission in cortical and hippocampal neurons. Specific projects include:
Presynaptic HCN channels and neuronal excitability
We have demonstrated that HCN channels are located at certain glutamatergic synaptic terminals in the adult entorhinal cortex inhibit synaptic release by restricting the activity of low threshold T-(CaV3.2) Ca2+ channels. Interestingly, the expression of pre- and post-synaptic HCN channels in the entorhinal cortex is differentially regulated. We are now using a combination of multi-photon imaging and electrophysiology to investigate which particular cortical neurons express pre-synaptic HCN channels and the cellular mechanisms that dictate which synapses may preferentially express these channels.
Function and Regulation of Axonal KV7 channels
Mutation in two types of KV7 subunits (KV7.2 and KV7.3) have been associated with Benign Familial Neonatal Convulsions (BFNC). Recent evidence shows that these KV7 subunits are targeted to the axon initial segments of hippocampal and cortical pyramidal neurons. KV7 mutations that cause BFNC impair axonal targeting of these channels. We have determined that the KV7 channels located at the axon initial segments of hippocampal pyramidal and granule cells regulate the action potential threshold and, thereby, neuronal firing. Interestingly, neurotransmitters such as acetylcholine cause long-term plasticity of these axonal KV7 channels. We are currently investigating the mechanisms by which neurotransmitters may regulate axonal KV7 channel activity and the impact of this on neuronal and network excitability.
In addition to being present on axon initial segments, KV7 channels are also found on axon nodes of Ranvier and synaptic terminals. We are interested in understanding how these channels contribute to information processing within axons and synaptic release.
T-type Ca2+ channels and medial entorhinal cortical stellate neuron excitability.
Layer II stellate neurons within the medial entorhinal cortex play a significant role in spatial information processing. Their properties vary along the dorsal-ventral axis. A contributing factor is the higher density and/or altered biophysical characteristics of voltage-gated K+ and HCN channels. We have found, though, that T-type Ca2+ channel function differentially affect dorsal and ventral medial entorhinal cortical stellate neuron function. We are currently exploring the underlying mechanisms for this.
- University College London
- Doctorate, Doctor of Philosophy | 2000
- University of Bath
- First Degree, Bachelor of Science (Honours) | 1997
Professor Mala Shah obtained a First Class (Hons) BSc in Pharmacology from the University of Bath, followed by a PhD at the Department of Pharmacology, University College London during which time she carried out work on characterising the slow afterhyperpolarization in hippocampal neurons. She subsequently won a Wellcome International Prize Travel Research Fellowship to work in Professor Daniel Johnston’s laboratory at Baylor College of Medicine (Texas, USA) where she started her work on understanding ion channel properties and function in entorhinal cortical dendrites under physiologic and epileptic conditions. In 2004, she returned to the Department of Pharmacology, University College London as a Senior Research Fellow in Professor David Brown’s laboratory and continued her studies on the functional significance of subcellular distribution of ion channels in hippocampal and cortical neurons during normal and epileptogenic conditions through funding received from the Wellcome Trust and Epilepsy Research Foundation. In 2007 she won the prestigious MRC New Investigator Award and joined the Pharmacology Department at UCL School of Pharmacy as a lecturer. In 2010, she obtained the esteemed ERC Starter Independent Grant.