Cellular and Systems Neuroscience

Mentor Areas

The lab’s efforts arise from the hypothesis that fundamental mechanisms underlie the communication and adaptability of the nervous system. Those same cellular mechanisms that normally serve the brain are misdirected and damaged during disease and are commandeered and altered by drugs during addiction. Therefore, fundamental mechanisms underlying neuronal function offer points of entry for pharmacological, physiological, and genetic methods aimed at relieving or preventing abnormal behaviors of mental disease and drug addiction. From this research prospective, the laboratory has made contributions toward our understanding or treatment of degenerative diseases, learning and memory, mood disorders, and addiction. Much of our effort in the last decade has been in the fields of dopaminergic and nicotinic cholinergic signaling (Nature Neuroscience 2001, 4:1224). For example, we have shown that addictive drugs induce synaptic potentiation of dopamine pathways as an early step along the route to addiction (Neuron 2009, 63:673) and that antidepressant therapies alter the signaling relationship between dopamine and serotonin systems (Neuron 2005, 46:65). We are also investigating memory functions of the hippocampus and midbrain during exposure to drugs and stress or during degenerative disease (e.g., Neuron 2013, 79:530), such as Parkinson’s disease and Alzheimer’s dementia. Work in the laboratory employs a multidisciplinary approach using cellular and higher-level physiological and biophysical systems techniques. The lab applies various electrophysiological techniques, optical signaling, immunocytochemistry, and amperometric/voltammetric measures of neurotransmitter release. We employ simplified systems, such as tissue culture and brain slices, to gain experimental advantages while investigating the mechanisms of ion channels, receptors, synapses, neurons, and small collections of neurons. In addition, the lab possesses a powerful arsenal of in vivo recordings techniques to examine the mechanisms underlying behavior. We apply these in vivo techniques to freely-moving rats and mice while they perform pertinent behavioral tasks, but occasionally anesthetized preparations are also used to gain experimental advantages. We now routinely apply microdialysis and HPLC to follow neurotransmitter levels, and this and related methods are used to apply drugs and signaling molecules to specific local areas within the brain. In addition, we are using multiple kinds of in vivo electrophysiological techniques coupled to molecular approaches to manipulate signaling molecules. Another extremely valuable approach is to stimulate a particular neural pathway and record the local field potential within brains of freely-moving rats and mice. This methodology allows us to perform many of the experiments that have only previous been performed in brain slices, but we obtain the data from freely-moving rodents over the course of months. As an example of the results, we have monitored the synaptic changes (as they occur) during drug-linked associative memory (Neuron 2009, 63:673). These are exciting new kinds of experiments that provide a low level endophenotype for synaptic events that are much nearer to the underlying genomic and proteomic signals than are the higher level behaviors or symptoms of genetic manipulations. The most powerful and demanding in vivo technique is the application of multiple tetrodes to follow many neuronal units while also stimulating and recording field responses. This methodology enables us to follow dozens of individual neurons in a circuit or in related separate circuits during behavioral events. Our recent efforts showed that dopamine signaling to the dorsal striatum and nucleus accumbens are decoded differently (J Neurosci. 2009, 29:4035). Those dopamine signaling differences are a fundamental signaling aspect associated with nicotine addiction (Nature Neurosci. 2001 4:1224). The most recent in vivo technique being established in my lab is to use carbon-fiber electrodes to measure catecholamine concentrations using fast-scan cyclic voltammetry. This method enables us to follow dopamine or serotonin concentration changes on the sub-second time scale within small target areas of the brain while animals that serve as models of disease perform behavioral tasks. Arising from our new efforts, the lab has one of the most diverse and powerful arrays of in vitro and in vivo physiological/biophysical techniques available.

Description:

1. Synaptic Neurophysiology underlying Learning and Memory.2. Cellular and Behavioral Mechanisms underlying Addiction.3. Consequences of Adolescent Nicotine on Brain Circuitry and subsequent Addictions.4. Impact of Stress on Circuitry and Behavior in Rodent Models.

Preferred Qualifications

There is a required training period. Therefore, your skills will be advantageous but not required. Also, we only take those students who will do longer-term times in the lab. Meetings for 2020-2021 academic year will be entirely online.