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Gary
Aston-Jones, Ph.D.
Dept. Psychiatry
705 Steller Chance Building
(215) 573-5200 fax (215) 573-5202
email: gaj@mail.med.upenn.edu
Positions Available
More on the Aston-Jones Lab: http://www.med.upenn.edu/astonjoneslab/
Click here for selected publications since Dr. Aston-Jones' arrival at Penn RESEARCH INTERESTS
Neurobiology of attention, affect, motivation and reward. Focus on neuromodulatory systems of norepinephrine, dopamine, and cholinergic neurons. Drug abuse, attention deficit disorder and stress/depression.RESEARCH TECHNIQUES
Neurophysiology in behaving animals and brain slices. Neuroanatomy (tract-tracing, transsynaptic tracing, immunohistochemistry), neuropharmacology of single neurons in vitro and in behaving animals.RESEARCH SUMMARY
My major research interest is the role of brainstem neuromodulatory systems in attention, affect and motivation. These interests have led me to focus on monoamine neurons that project to the forebrain, especially with regard to their role in mental functions and dysfunctions. The major approach is to characterize physiologic, anatomic, pharmacologic and behavioral properties of neurons in those circuits. Currently there are three lines of work being pursued most intensively:
Role of brain neuromodulatory systems in cognitive function. Electrical activity of noradrenergic locus coeruleus (LC) neurons is recorded in monkeys performing an attention task. We find that these neurons are activated phasically by CS+ stimuli, and vary their tonic activity closely with measures of focused attention. Together, these results indicate that the LC may play a role in selective attention and attentional shifting, and support previous hypotheses of LC's involvement in attentional disorders. My colleagues and I constructed a neural network model which simulates LC activity recorded in monkeys performing this task, and the relationship between LC activity and the level of task performance. Moreover, this model makes several predictions concerning mechanisms responsible for the role of LC in this task which are being tested in ongoing work. Recent results indicate that inputs from cortical regions (e.g., anterior cingulate cortex) may be important for regulating LC function in attentional processes.
Afferent regulation of noradrenergic locus coeruleus neurons. Anatomical, physiological and pharmacological studies are aimed at discerning what brain areas control activity of LC neurons. Results indicate that direct afferents to the LC nuclear core are more restricted than previously thought, and dense inputs originate from the ventrolateral and dorsomedial rostral medulla. However, a distinct afferent channel to LC dendrites may exist to modulate the effectiveness of these nuclear inputs. We are also using viral transsynaptic tracing and electrophysiology to investigate multisynaptic afferent circuitry underlying functional properties of LC neurons. Results with this technique indicate that the suprachiasmatic nucleus is a prominent indirect input to the LC, revealing a circuit for circadian regulation of alertness and attentional processes. Finally, experiments are also underway to identify afferents to the locus coeruleus in monkey.
Role of the dopaminergic and noradrenergic systems in drug abuse. Studies in brain mechanisms underlying drug abuse include behavioral pharmacology, electrophysiology in waking and anesthetized animals as well as in in vitro brain slices, localization of immediate early gene products such as Fos, and tracing connections anatomically among brain areas involved. These experiments reveal that systemically administered beta adrenergic antagonists attenuate anxiogenic behaviors characteristic of opiate withdrawal and cocaine abstinence, as well as somatic and aversive signs of opiate withdrawal. A combined neuroanatomical and behavioral study revealed that beta receptors in the bed nucleus of the stria terminalis are critical for the aversive property of morphine withdrawal, and identified the source of the NE for this effect to the nucleus tractus solitarius (A2 group). Also, recent experiments indicate an important role of the DA innervation of the accumbens in opiate withdrawal. Current studies are investigating interactions between NE and DA systems in opiate withdrawal. Finally, recent results have led to new proposals for the use of serotonergic or dopaminergic agonists for the treatment of opiate abuse.
Positions Open
Staff/Research Associate Position: available April 1, 2003 to study brain mechanisms of drug abuse in rat. PhD and experience in behavioral pharmacology of drug abuse required. Duties include experimental design, oversight of technical personnel, surgery for intracranial implants, behavioral conditioning, data analysis and preparation of manuscript drafts. Funded by new 5 yr NIH award; excellent Penn benefits.
