Led by principal investigator Michael Friedlander, Ph.D., the Friedlander Lab studies the processes that regulate alterations in synaptic efficiency between neurons within the cerebral cortex — synaptic plasticity — and how these cellular processes are affected during brain development, after experiences including learning, and in response to brain injury.
The Friedlander Lab uses quantitative single neuron patch clamp electrophysiological methods along with cellular and subcellular imaging to visualize the changes in structure and calcium signals that underlie alterations in functional synaptic connectivity within the mammalian neocortex. This work is carried out in vitro in acute living brain slice preparations with simultaneous whole cell patch clamp recording from multiple cortical neurons that are synaptically interconnected. This approach allows for the application of quantal analysis to determine how the induction of synaptic plasticity affects a variety of components of synaptic transmission, including probability of presynaptic neurotransmitter release in response to a single action potential in an individual cortical neuron and the quantal size or postsynaptic neurotransmitter receptor availability.
- Apparently like-type sets of interconnected cortical neurons exhibit wide variability in their baseline synaptic transmission properties, and in their plasticity behavior in response to an identical synaptic conditioning protocol. The Friedlander Lab is currently studying the origin of the variability of synaptic plasticity between different sets of cortical synapses of otherwise like-type, specifically evaluating to what degree intrinsic differences in gene expression versus environmental activity during early brain development and throughout life modify the capacity, likelihood and polarity of changes in synaptic efficiency.
- The temporal patterns of incoming synaptic activity impinging onto a single neocortical neuron can differentially modulate plasticity responses, even when the overall frequency of the activation is identical. The Friedlander Lab uses this approach to explore plasticity induction processes in the normal brain and after brain injury. This line of investigation is also aimed at identifying specific patterns of synaptic activation that are most effective at accessing the downstream plasticity signaling pathways in the injured brain as an approach to neurorehabilitation.