Division of Sleep Medicine @ Harvard Medical School
Faculty Profile
James Timothy McKenna, PhD
Instructor in Psychiatry, Harvard Medical School
Research Scientist, Department of Psychiatry, VA Boston Healthcare System
Society Memberships
Sleep Research SocietySociety for Neuroscience
Research Unit(s)
Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System
Research Interests
Dr. McKenna’s research investigates how brain neurotransmitter systems control the sleep-wake cycle, employing the rodent model. Such research may provide a basis for the understanding of human sleep disorders, such as obstructive sleep apnea (OSA), narcolepsy, and insomnia. The knowledge gained from these investigations may directly inform the development of treatments.
Dr. McKenna employs a number of techniques in his research, including microdialysis, HPLC (high performance liquid chromatography), ELISA, EEG/EMG recording and analysis, neuroanatomical tract tracing, and immunohistochemistry. His initial research at Harvard Medical School included measurement of levels of the purine nucleoside adenosine, an indicator of sleepiness. Extracellular fluid was collected from sleep-related brain nuclei and analyzed by means of HPLC. Both a circadian rhythm of adenosine levels, as well as a rise in adenosine levels due to sleep deprivation, was observed in the rodent basal forebrain. These findings imply that basal forebrain adenosine levels may reflect the sleep drive that occurs in animals exhibiting a diurnal pattern of sleep and wakefulness. In another study, the laboratory measured extracellular serotonin release, by means of microdialysis and HPLC, following infusion of the neuropeptides orexin-A or –B into the median raphe and dorsal raphe nuclei. The orexins were found to have a regionally selective effect on serotonin release in the CNS, implying an interaction between the two neurotransmitter systems in regulation of sleep and wakefulness.
In his graduate studies at Florida Atlantic University, Dr. McKenna investigated neural circuitry by means of tract tracing. Since joining Harvard Medical School, he has focused on neuroanatomical investigations of brain circuitry involved in behavioral state control (wake, NREM sleep, and REM sleep). For instance, he recently developed studies employing a novel mouse model in which a green fluorescent protein is expressed in knock-in mice (specifically expressed in GABAergic neurons). This allowed investigation of the neurotransmitter GABA, and its unique role in the control of vigilance states. Dr. McKenna plans to further develop these studies, as well as other investigations into the different types of neurons and neurotransmitters related to sleep-related brain circuitry, at times using unique rodent models.
OSA is a disorder that afflicts 4% of the general population, and up to 20% of the aging male population, with sleepiness, cognitive impairment and cardiovascular abnormalities. OSA is characterized by a collapse of the upper airway passage during sleep. These events lead to a brief arousal to reestablish airflow. This disorder can be separated into two primary characteristics: intermittent hypoxia and sleep fragmentation. Dr. McKenna participated in the development of novel animal models of these OSA symptoms, and further extended this research into a successful Ruth L. Kirschstein National Research Service Award. He documented sleepiness by means of neurochemical and electrographic analysis. For instance, novel measurements of sleepiness were developed, including a rat multiple sleep latencies test, which provided an objective and robust measure of sleepiness. Dr. McKenna also conducted investigation of brain areas following exposure to the rodent OSA model, employing immunohistochemistry for documenting the phenotype of cells, apoptosis (cell death), and expression of c-Fos (a protein biomarker of neuronal activation). Dr. McKenna plans to continue developing unique models that will be useful to further understanding of the underlying biological mechanisms of sleep pathologies, as well as allow testing of therapeutic interventions.
Besides his research activities, Dr. McKenna has participated in the laboratory’s undergraduate internship program, where he acts as a mentor, assisting students from local universities to gain experience in laboratory research. He aims to provide a welcome environment, fostering students’ interests in biology, neuroscience and basic sleep research. Dr. McKenna also taught undergraduate Neuroscience as an adjunct professor at Stonehill College in the Department of Biology. He brings to the classroom much enthusiasm concerning the subject matter of neuroscience, biology, psychology, and statistics.
Dr. McKenna employs a number of techniques in his research, including microdialysis, HPLC (high performance liquid chromatography), ELISA, EEG/EMG recording and analysis, neuroanatomical tract tracing, and immunohistochemistry. His initial research at Harvard Medical School included measurement of levels of the purine nucleoside adenosine, an indicator of sleepiness. Extracellular fluid was collected from sleep-related brain nuclei and analyzed by means of HPLC. Both a circadian rhythm of adenosine levels, as well as a rise in adenosine levels due to sleep deprivation, was observed in the rodent basal forebrain. These findings imply that basal forebrain adenosine levels may reflect the sleep drive that occurs in animals exhibiting a diurnal pattern of sleep and wakefulness. In another study, the laboratory measured extracellular serotonin release, by means of microdialysis and HPLC, following infusion of the neuropeptides orexin-A or –B into the median raphe and dorsal raphe nuclei. The orexins were found to have a regionally selective effect on serotonin release in the CNS, implying an interaction between the two neurotransmitter systems in regulation of sleep and wakefulness.
In his graduate studies at Florida Atlantic University, Dr. McKenna investigated neural circuitry by means of tract tracing. Since joining Harvard Medical School, he has focused on neuroanatomical investigations of brain circuitry involved in behavioral state control (wake, NREM sleep, and REM sleep). For instance, he recently developed studies employing a novel mouse model in which a green fluorescent protein is expressed in knock-in mice (specifically expressed in GABAergic neurons). This allowed investigation of the neurotransmitter GABA, and its unique role in the control of vigilance states. Dr. McKenna plans to further develop these studies, as well as other investigations into the different types of neurons and neurotransmitters related to sleep-related brain circuitry, at times using unique rodent models.
OSA is a disorder that afflicts 4% of the general population, and up to 20% of the aging male population, with sleepiness, cognitive impairment and cardiovascular abnormalities. OSA is characterized by a collapse of the upper airway passage during sleep. These events lead to a brief arousal to reestablish airflow. This disorder can be separated into two primary characteristics: intermittent hypoxia and sleep fragmentation. Dr. McKenna participated in the development of novel animal models of these OSA symptoms, and further extended this research into a successful Ruth L. Kirschstein National Research Service Award. He documented sleepiness by means of neurochemical and electrographic analysis. For instance, novel measurements of sleepiness were developed, including a rat multiple sleep latencies test, which provided an objective and robust measure of sleepiness. Dr. McKenna also conducted investigation of brain areas following exposure to the rodent OSA model, employing immunohistochemistry for documenting the phenotype of cells, apoptosis (cell death), and expression of c-Fos (a protein biomarker of neuronal activation). Dr. McKenna plans to continue developing unique models that will be useful to further understanding of the underlying biological mechanisms of sleep pathologies, as well as allow testing of therapeutic interventions.
Besides his research activities, Dr. McKenna has participated in the laboratory’s undergraduate internship program, where he acts as a mentor, assisting students from local universities to gain experience in laboratory research. He aims to provide a welcome environment, fostering students’ interests in biology, neuroscience and basic sleep research. Dr. McKenna also taught undergraduate Neuroscience as an adjunct professor at Stonehill College in the Department of Biology. He brings to the classroom much enthusiasm concerning the subject matter of neuroscience, biology, psychology, and statistics.
Mentor(s)
Teaching
Adjunct Professor, Stonehill College, Dept. of Biology
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).
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
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.
In press, European Journal of Neuroscience, 2007.
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.
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.
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.
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 May;23(10):2739-48.
Strecker RE, Basheer R, McKenna JT, McCarley RW. Another Chapter in the Adenosine Story.
Invited Editorial, Sleep 2006; 29: 426-428.
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. [PMID: 15514932]
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]
In press, European Journal of Neuroscience, 2007.
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.
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.
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.
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 May;23(10):2739-48.
Strecker RE, Basheer R, McKenna JT, McCarley RW. Another Chapter in the Adenosine Story.
Invited Editorial, Sleep 2006; 29: 426-428.
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. [PMID: 15514932]
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]
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