Research Opportunities for Psychiatry Residents and Fellows
The Systems and Behavioral Neuroscience division of the Department of Neurobiology and Anatomy includes six laboratories, all of which study cellular, circuit, and neural network processes that underlie normal and maladaptive behaviors. Basic organization and operation of thalamocortical pathways, limbic circuits and central monoaminergic systems are the primary focus the of these research teams. Individual laboratories employ a variety of neurochemical, electrophysiological, neuroanatomical, computer modeling and behavioral assays, and conduct studies in both in vitro and in vivo preparations, including experiments in awake, behaving animals. The research teams in the group are composed of primary faculty, postdoctoral fellows, technicians, graduate students and visiting scholars. Individuals within the group are funded by grants from federal and private agencies including the National Institute of Mental Health and National Institute of Drug Abuse, and also by two NIH training grants that can support as many as eight postdoctoral fellows. The atmosphere is exciting and highly interactive with frequent collaborations between laboratories, several regularly scheduled journal clubs and a weekly seminar series. The laboratories are well equipped with state-of-the-art electrophysiology equipment and computer-based imaging systems. Psychiatry residents will be able to conduct basic research that contributes directly to a better understanding of a variety of psychiatric and behavioral disorders. The following are specific areas of concentration.
Stress/anxiety and depression
Drs. Page, Okere, Moxon
Recent studies suggest that the central monoaminergic pathways, in particular those using norepinphrine and serotonin as their transmitters, play a major role in mediating the stress response and the progression from episodes of acute trauma or repetitive stress to various forms of anxiety and depression. Moreover, many of the compounds used successfully to treat stress impact monoaminergic neurotransmission. A major thrust of the Systems and Behavioral Neuroscience group at Drexel Med are studies focusing on the basic neurobiology of the monoaminergic systems and their relationship to the stress response and the pathogenesis and treatment of anxiety and depression. For example, investigations using neurochemical (Dr. Page) and neuroanatomical (Dr. Okere) approaches have focused on the neural substrates of stress and anxiety as induced by forced swim test, restraint or capsaicin injection in laboratory rats. The results of Dr. Okere’s work implicate both the serotonergic and nitric oxide components of the dorsal raphe projection system in mediating the stress response. Dr. Page’s laboratory is using microdialysis in conjunction with HPLC-electrochemical detection as a means of measuring the ability of conventional SSRI’s and newer norepinephrine-selective reuptake blockers, e.g. reboxitine, to alter stress-evoked responses in acute and stress-conditioned animals. Dr. Page is also initiating studies that use multichannel, multineuron extracellular recording in waking animals to examine the response properties of prefrontal cortical neurons under conditions of acute stress and acute or chronic antidepressant drug administration. Dr. Moxon employs computer-based computational modeling techniques to examine the influence of synpatically-released norepinephrine on the dynamic response properties of thalamocortical networks. This is a powerful new approach that can be used to predict the actions and efficacy of conventional or novel monoamine-selective anti-depressant drugs. Many of the aforementioned research programs have direct application to clinical studies of post-traumatic stress disorder (PTSD) as conducted by Dr. Sue McLeer and colleagues in the Department of Psychiatry.
Drug abuse and addiction
Drs. Castro-Alamancos, Okere, Page, Shumsky, Waterhouse
Our department is also heavily invested in research directed at understanding the neuronal mechanisms underlying drug abuse, drug addiction, and drug craving. In particular, ongoing work focuses on acute and chronic actions of cannabinoids, opiates, cocaine, amphetamine, MDMA (Ecstasy) and nicotine in brain circuits that are densely innvervated by dopaminergic, noradrenergic and serotonergic projections from the ventral tegmental area, locus coeruleus and dorsal raphe nucleus, respectively. Dr. Waterhouse uses single neuron and multichannel, multineuron extracellular recording techniques to investigate the actions of cocaine and nicotine on single cell and neural circuit functions in awake and anesthetized preparations. Dr. Onn takes advantage of her expertise in patch clamp and intracellular recording procedures (both in vitro and in vivo) to study the actions of acute and chronic nicotine and amphetamine on prefrontal cortical cell and circuit operations. Drs. Okere and Shumsky use neuroanatomical techniques to characterize responses of selected populations of cortical and dorsal raphe neurons to acute, chronic or in utero exposure to cocaine, amphetamine and MDMA (Ecstasy). Finally, Dr. Page is using microdialysis-HPLC electrochemical detection to determine the effect of cannabinoid on central levels of norepinephrine. The overall goal of these investigations is to gain insights into the mechanisms through which drugs of abuse produce their desirable effects and promote persistent, deleterious changes in brain circuitry and behavior. The hope is that such new knowledge will lead to more effective prevention and treatment of drug abuse and drug addiction.
ADHD and Autism spectrum disorders
Drs. Castro-Alamancos, Moxon, Page, Shumsky, Waterhouse
One of the hallmarks of many psychiatric disorders is inappropriate processing and/or behavioral response to salient emotional or environmental stimuli. Many of the researchers in the Department of Neurobiology and Anatomy are, in fact, engaged in studies that seek clarification of the mechanisms normally responsible for state dependent regulation of signal transfer through neural networks. For example, electrophysiological and neuroanatomical investigations by Waterhouse and colleagues, spanning a period of >20 years, indicates that the central monoaminergic systems exert powerful modulatory influences on behavioral state and state-dependent cognitive processes via actions at both cellular and neural circuit levels. Drs. Castro-Alamancos and Moxon are making concerted efforts to understand how information is transmitted and processed by local thalamic and cortical circuits and the thalamocortical network as a whole during various stages of sleep and arousal. Dr.Shumsky uses a behavioral assay to identify factors that influence animal performance on a sustained attention task.
The findings of all of the above studies have direct implications for understanding the biological basis of many psychiatric disorders. Moreover, the experimental strategies developed in these investigations are readily adapted to projects that can directly test the actions of commonly used psychopharmacologic agents. For example, ongoing work by Waterhouse and colleagues is providing new information about the biological basis of ADHD by investigating the effects of methylphenidate (Ritalin) on signal transmission through thalamocortical sensory circuits of the rat brain. Much of this work is carried out using state-of-the-art multi-channel, multi-neuron recording procedures in awake, freely moving animals. Likewise, computer modeling studies by Dr. Moxon have extended our understanding of psychostimulant influences on large arrays of neurons that receive and process sensory inputs. Drs. Shumsky and Waterhouse are making plans to measure the effects of amphetamine-like stimulants, including methylphenidate, on animal performance in the rodent sustained attention task.
Another emerging research theme for this group is autism spectrum disorders. These genetically-based developmental disorders begin in early life and affect a person’s ability to communicate, interact with other people and maintain normal contact with the outside world. In addition, there is a significant component of sensory deficit and/or perception in these individuals. The neural substrates underlying these disorders are largely unknown, but there is general agreement that abnormal function of dopamine and serotonin systems in the forebrain is a key component of the pathophysiology. Treatment often includes anti-psychotic medications such as olanzepine and ziprasodone that are known to interact with these putative transmitters systems. The Systems and Behavioral Neuroscience group is planning studies where the actions of antipsychotic medications that prove effective in treating autism spectrum disorders are examined in dopamine and serotonin circuits of the brain. Other work will focus on the basic function of dopamine and serotonin systems in brain areas associated with the behavioral symptoms of autism. This group is well suited to pursue this line of investigation and will provide a strong complement to the clinical research efforts in autism spectrum disorders led by Dr. Richard Malone of the Department of Psychiatry.