Leena Williams

A pivotal question to understanding brain function is to illuminate how neuronal brain circuits adapt to support behavior.  Sensory perception is thought to be associated with brain plasticity, i.e. a strengthening or weakening of synaptic connections between neurons. Throughout my career my interest has been to unravel the circuit mechanisms underlying brain plasticity and to reveal its’ role in sensory experience.

            Prior to my PhD, I was a Research Coordinator in Neurosurgery researching cutting-edge experimental methods for treating inoperable brain tumors which compelled me to pursue a doctorate in Neurobiology. While earning my PhD in Prof. David Featherstone’s laboratory at the University of Illinois at Chicago, I revealed that glia regulate neurotransmission and demonstrated that extracellular glutamate, beyond the synaptic cleft, is critical for maintaining synaptic homeostasis and synaptic strength (Williams L.E. & Featherstone D.E., JNS 2014).

            To deepen my knowledge of plasticity, I moved to Switzerland to do a Post-doc with Prof. Anthony Holtmaat at the University of Geneva.  I discovered that plasticity can be elicited in pyramidal neurons (PN) of the somatosensory cortex (S1) upon the paired activation of incoming sensory inputs to the cortex and higher-order, top-down inputs from thalamus.  Further dissection of the synaptic circuitry uncovered that this is critically gated by activation of inhibitory interneurons or cells that dampen down excitation. This motif may allow contextual feedback, from the higher-order thalamus, to shape synaptic circuits that process first-order sensory information (Williams L.E. & Holtmaat A.H., Neuron 2019; Lewis S. Nat Rev Neurosci. 2019). This landmark study soon made me want to understand what happens when these cortical circuits are dysfunctional? How does this impact sensory experience and mental health?

            It is known that sensory, e.g. touch, sensitivities are a prevalent and understudied feature of many neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). In 2019, I was awarded a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation to study cortical circuit impairments in autism.  I soon joined the Simons Initiative for the Developing Brain to combine my expertise in cortical circuits and plasticity with world-leading experts in autism.   Since arriving at SIDB, I have been consistently impressed with the collaborative spirit and was recently awarded a Discovery Fellowship with the Biotechnology & Biological Sciences Research Council.  In future, my research could reveal that impairments in synaptic plasticity and the underling neuronal circuitry may underpin tactile hypersensitivities in autism.

• Synaptic plasticity mechanisms underpinning sensory gating and perceptual learning in the somatosensory cortex. 
• Impact of cortical circuit dysfunction on sensory experience. 
• Unraveling the cortical circuit dysfunction underpinning tactile impairments in rodent models of autism. 

Contact: [email protected]