Faculty Profile

James Timothy McKenna, PhD

J. Timothy McKenna, PhD profile photo
Assistant Professor, Harvard Medical School
Research Scientist, Department of Psychiatry, VA Boston Healthcare System

See publications

Email james_mckenna@hms.harvard.edu

Society Memberships

Society of Neuroscience
Sleep Research Society

Research Unit(s)

Research Interests

Dr. McKenna is an Assistant Professor in the Department of Psychiatry and Director of the Neuroanatomy Section of the Laboratory of Neuroscience. His research investigates sleep-wake regulation and disorders in animal models, employing neuroanatomical, neurochemical, electrophysiological, and behavioral measures.

One focus of Dr. McKenna’s research has been the validation and use of a novel mouse model in which green fluorescent protein is expressed in GABAergic neurons. He described for the first time the morphology and location of GABAergic neurons involved in REM sleep control and cortical activation in the mouse. Using retrograde tracing methods, Dr. McKenna identified interconnections between these GABAergic neurons and other sleep control-related nuclei. These findings may inform the development of compounds to treat sleep disorders, since GABAergic neurotransmitter systems are a target of hypnotics and anesthetics.

Another line of Dr. McKenna’s research is the evaluation of animal models of sleep disorders, such as obstructive sleep apnea, narcolepsy, and insomnia. Sleep apnea is a disorder that afflicts 7% of the adult population, with sleepiness, cognitive impairment and cardiovascular consequences. Dr. McKenna has been instrumental in the development and evaluation of novel models of sleep apnea characteristics, including hypoxia (low oxygen levels), hypercapnia (high carbon dioxide levels), and sleep disruption. These studies were extended into a National Research Service Award, in which Dr. McKenna demonstrated apoptosis and neuronal dysregulation in cognition-related neural circuitry. He showed that sleep disruption, mimicking that seen in the apneic patient, produced excessive sleepiness and cognitive impairment. Sleep disruption produced a rise of levels of the neuromodulator adenosine in the wake-promoting basal forebrain, providing a mechanism whereby sleep disruption leads to sleepiness. Dr. McKenna employed other measures of sleepiness, including a novel rat sleep latencies test (mimicking the human diagnostic tool), now employed by other investigators. He recently validated an animal model of hypercapnia, which is the central experimental manipulation in a recently funded program project grant.

As the laboratory’s neuroanatomist, Dr. McKenna provides expert validation of the physiological and behavioral findings of the laboratory, evident in his role as investigator on five laboratory grants and numerous collaborative publications. For example, Dr. McKenna described the neurotransmitter profile of the prefrontal cortex, essential for the laboratory’s in vitro murine model of schizophrenia gamma oscillation abnormalities. He also validated viral transfection in recent optogenetic studies, therefore allowing investigation of wake-promoting neurons in the basal forebrain using this innovative technique.

Contributions to teaching and education include lectures at Harvard Medical School, as well as training of post-docs in the laboratory. Dr. McKenna has mentored many undergraduate interns, some of whom were authors on conference presentations and publications. These students contribute greatly to funded laboratory projects, performing extensive microscopic analysis. Many have continued in science-related careers, and one past intern recently received a Fulbright scholarship. In summary, Dr. McKenna’s innovative research provides a basis for the understanding of sleep-wake regulation and human sleep disorders, and may provide knowledge that may inform the development of therapeutic treatments.


Honors and Awards
Completed the Training Program in Sleep, Circadian and Respiratory Neurobiology at Harvard Medical School, Department of Medicine, Division of Sleep Medicine (2002-2004).

Selected Publications

Peer reviewed publications in print or other media

Research Investigations
Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness.
Physiol Rev, 2012. In press.

McKenna JT, Christie MA, Jeffrey BA, McCoy JG, Lee E, Connolly NP, Ward, CP, Strecker RE. Chronic ramelteon treatment in a mouse model of Alzheimer’s disease.
Archives Italiennes de Biologie, 2011. In press.

McNally JM, McCarley RW, McKenna JT, Yanagawa Y, Brown RE. Complex receptor
mediation of acute ketamine application on in vitro gamma oscillations in mouse prefrontal cortex: modeling gamma band oscillation abnormalities in schizophrenia.
Neuroscience. 2011 Dec 29;199:51-63. Epub 2011 Oct 19. [PMID: 22027237]

Chen L, McKenna JT, Bolortuya Y, Winston S, Thakkar MM, Basheer R, Brown RE, McCarley RW. Knockdown of orexin type I receptor in rat locus coeruleus increases REM sleep during the dark period.
European Journal of Neuroscience 2010, 32:1528-36. [PMID: 21089218]

McCoy JG, McKenna JT, Connolly NP, Poeta DL, Ling L, McCarley RW, Strecker RE. One week of exposure to intermittent hypoxia impairs attentional set-shifting in rats.
Behavioral Brain Research 2010, 210: 123-6. [PMID: 20122971]

Chen L, McKenna JT, Leonard MZ, Yanagawa Y, McCarley RW, Brown RE. GAD67-GFP knock-in mice have normal sleep-wake patterns and sleep homeostasis.
Neuroreport 2010, 21:216-20. [PMID: 20051926]

Tartar JL, McKenna JT, Ward CP, McCarley RW, Strecker RE, Brown RE. Sleep fragmentation reduces hippocampal CA1 pyramidal cell excitability and response to adenosine.
Neuroscience Letters 2010, 469: 1-5. [PMID: 19914331]

Ward CP, McCoy JG, McKenna JT, Connolly NP, McCarley RW, Strecker RE. Spatial learning and memory deficits following exposure to 24 h of sleep fragmentation or intermittent hypoxia in a rat model of obstructive sleep apnea.
Brain Research 2009, 1294: 128-137. [PMID: 19643093]

McKenna JT, Cordeira JW, Jeffrey BA, Ward CP, Winston S, McCarley RW, Strecker
RE. c-Fos protein expression is increased in cholinergic neurons of the rodent basal forebrain during spontaneous and induced wakefulness.
Brain Res Bull. 2009 Dec 16;80(6):382-8. Epub 2009 Aug 28. [PMID: 19716862]

Christie MA, Bolortuya Y, Chen LC, McKenna JT, McCarley RW, Strecker RE. Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat psychomotor vigilance task.
Sleep 2008, 31: 1393-8.[PMID: 18853936]

Christie MA, McKenna JT, Connelly NP, McCarley RW, Strecker RE. 24-hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task.
Journal of Sleep Research 2008: 17: 376-84. [PMID: 19021853]

McKenna JT, Cordeira JW, Tartar JL, McCoy JG, Lee E, McCarley RW, Strecker RE. Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness.
Journal of Sleep Research 2008, 17: 365-375. [PMID: 18823428]

Brown RE, McKenna JT, Winston S, Basheer R, Yanagawa Y, Thakkar MM, McCarley RW. Characterization of GABAergic neurons in rapid-eye-movement (REM) sleep controlling regions of the brainstem reticular formation in GAD67-GFP knock-in mice.
European Journal of Neuroscience 2007, 27: 352-363. [PMID: 18215233]

McKenna JT, Tartar JL, Ward CP, Thakkar MM, Cordeira JW, McCarley RW, Strecker RE. Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness. Neuroscience 2007, 146:1462-73. [PMID: 17442498]

McCoy JG, Tartar JL, Bebis AC, Ward CP, McKenna JT, Baxter MG, McGaughy J, McCarley RW, Strecker RE. Experimental sleep fragmentation impairs attentional set-shifting in rats.
Sleep 2007, 30:52-60. [PMID: 17310865]

Tao R, Ma Z, McKenna JT, Thakkar MM, Winston S, Strecker RE, McCarley RW. Differential effect of orexins (hypocretins) on serotonin release in the dorsal and median raphe nuclei of freely behaving rats.
Neuroscience 2006, 141:1101-5. [PMID: 16820265]

Tartar J, Ward C, McKenna J, Thakkar M, Arrigoni E, McCarley R, Brown R, Strecker R. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.
European Journal of Neuroscience 2006, 23:2739-48. [PMID: 16817877]

Strecker RE, Basheer R, McKenna JT, McCarley RW. Another Chapter in the Adenosine Story.
Sleep 2006, 29: 426-428. [PMID: 16676774]

Ma Z, Strecker RE, McKenna JT, Thakkar MM, McCarley RW, Tao R. Effects on serotonin of(-) nicotine and dimethylphenylpiperazinium in the dorsal raphe and nucleus accumbens of freely behaving rats.
Neuroscience 2005, 135: 949-958.[PMID: 16154286]

McKenna JT, Vertes RP. Afferent projections to the nucleus reuniens.
Journal of Comparative Neurology 2004, 480: 115-142.

McKenna JT, Dauphin LJ, Mulkern KJ, Stronge AM, McCarley RE, Strecker RE. Nocturnal elevation of extracellular adenosine in the rat basal forebrain.
Sleep Research Online 2003, 5: 155-160.

McKenna JT, Vertes RP. Collateral projections from the median raphe nucleus to the medial septum and hippocampus.
Brain Research Bulletin 2001, 54: 619-630. [PMID: 11403988]

Vertes RP, McKenna JT. Collateral projections from the supramammillary nucleus to the medial septum and hippocampus.
Synapse 2000, 38: 281-293. [PMID: 11020231]

Other Peer-reviewed Publications
Chen L, Brown RE, McKenna JT, McCarley RW. Animal models of narcolepsy.
CNS and Neurological Disorders: Drug Targets 2009, 8: 296-308.

Non-peer reviewed scientific or medical publications/materials in print or other media

Reviews, chapters, monographs and editorials

Strecker RE, McKenna JT. Neurochemistry of wakefulness and sleep.
In: Stimulant Medications and Cognitive Performance. Wesensten N (Ed.), 2011. Cambridge University Press, UK. In press.

McKenna JT, Chen L, McCarley RW. Neuronal models of REM sleep control: evolving concepts. In: Rapid Eye Movement Sleep: Regulation and Function. Mallick BN, Pandi-Perumal SR, McCarley RW, Morrison AR (Eds.), 2011. Cambridge University Press, UK.

McKenna JT, Brown RE, McCarley RW. Neuroanatomy and neurobiology of sleep and wakefulness.
In: Foundations of Psychiatric Sleep Medicine. Plante DT, Winkelman J (Eds.), 2010. Cambridge University Press, UK.

Basheer R, McKenna JT, McCarley RW. Pharmacology of Sleep: Adenosine.
In: The Neuroscience of Sleep. Stickgold R and Walker M (Eds.), 2009. Elsevier, USA

Basheer R, McKenna JT, McCarley RW. Pharmacology of Sleep: Adenosine.
In: Encyclopedia of Neuroscience, Squire LR (Ed.), 2009. Oxford: Academic Press, UK and Elsevier, USA.

McKenna JT. A Neuroanatomical Investigation of the Median Raphe Nucleus, Supramammillary Nucleus, and Nucleus Reuniens: Possible Implications for the Modulation of the Hippocampal EEG. Florida Atlantic University, Charles E. Schmidt College of Science, Center for Complex Systems and Brain Sciences. December, 2001.

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