Ronald B. Langdon, PhD
Associate Professor
Major research interests:
- the physiology and pharmacology of excitatory neurotransmission in the hippocampus and neocortex;
- activity-dependent synaptic plasticity in development and adult learning and memory;
- excitotoxicity and neurodegeneration.
- physiological brain slices prepared acutely from the neocortex and hippocampus;
- extracellular and intracellular (patch-clamp) recording;
- transgenic mouse models of human disease;
- neuronal reconstruction;
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In the brains of humans and animals, neurons communicate with each other via specialized points of contact called "synapses", where information is passed rapidly from one nerve cell to the next via a sequence of bioelectric and neurochemical events referred to as "synaptic transmission" (or "neurotransmission"). There are two basic kinds of synaptic transmission, excitatory and inhibitory, and brain function absolutely depends on both throughout every moment of our lives, while awake and asleep. Excitatory neurotransmission is essential because it provides our neuronal networks with the drive that makes them active, and inhibitory neurotransmission is essential because it prevents our brains from being overwhelmed by uncontrolled propagation of impulses from one neuron to the next.
In the Laboratory of Cellular and Synaptic Neurophysiology, we conduct research aimed at improving our understanding of central excitatory neurotransmission and its "plasticity" in health and in disease. From our own research, and that which has been done by a large number of other neuroscientists working over the past several decades, it is clear that excitatory synaptic connection strengths are constantly being adjusted upward and downward during normal brain function, and these adjustments are based on patterns of synapse use and postsynaptic activity. It is also known that this plasticity is an essential part of the process whereby our brains develop and mature, and it is further believed by many to be integral to our ability to learn and remember new information and skills throughout life.
Long-term potentiation (LTP). Much of the research conducted in our laboratory has been concerned with a particular form or model of activity-dependent synaptic plasticity known as "long-term potentiation" (LTP). Long-term potentiation is of widespread interest among neuroscientists because it is induced, expressed, and maintained by cellular mechanisms that may enable synchronously active neurons in vivo to join together and form functional co-active neuronal networks. Our research has examined the specific conditions under which LTP occurs in the hippocampus and the neocortex, and has characterized a change in neuronal network activity when it is expressed in the neocortex. Some of our experiments have been done in physiological "brain slices" derived from "wild-type" rats and mice, and these had the goal of defining basic properties of LTP and other forms of synaptic plasticity as they occur in animals that have not been subjected to any direct genetic manipulation (e.g., Langdon et al., 1993, 1995; Walcott and Langdon, 2001, 2002). Other studies have been done using genetically altered mice in which a normally present part of the genome has been deleted (Holst et al., 1998; Feng et al., 2001). The purpose of these experiments was to determine whether the specific gene deletions either enhanced or interfered with the capability for LTP, which could then be associated with abnormal brain development or defects in adult learning.
Excitotoxicity and neurodegeneration. Even though excitatory synaptic transmission is essential for brain function, a careful balance must be maintained in the nervous system because too much excitatory drive is deadly to neurons. When damage to neurons is caused by excessive excitatory input, this is referred to as "excitotoxicity", and it is known to be mediated by excessive exposure of neurons to the excitatory neurotransmitter glutamate. Acute glutamatergic excitotoxicity is clearly an important cause of neuronal damage and death during catastrophic events in the brain and spinal cord, such as stroke, physical trauma, and certain forms of epileptic seizure. Chronic, low-level excitotoxicity has also been proposed to play an important role in some of the more devastating of the neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Our laboratory has recently undertaking an initiative to examine the validity of this latter hypothesis, and address the question of how cellular neurophysiology is altered by this chronic excitotoxicity, if the hypothesis is correct.