Division of Sleep Medicine @ Harvard Medical School
Faculty Profile
James Timothy McKenna, PhD
Instructor in Psychiatry, Harvard Medical School
Instructor in Psychiatry, Department of Psychiatry, Harvard Medical School
Research Scientist, Department of Psychiatry, VA Boston Healthcare System
Society Memberships
Sleep Research SocietyAmerican Academy of Sleep Medicine
Society of Neuroscience
Research Unit(s)
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, behavioral testing, 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.
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, behavioral testing, 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.
Mentor(s)
Ritchie E. Brown, PhD; Robert E. Strecker, PhD; Robert W. McCarley, MD
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
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]
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 Res. 2009 Oct 19;1294:128-37. Epub 2009 Jul 28. [PMID: 19643093]
Chen L, Brown RE, McKenna JT, McCarley RW. Animal models of narcolepsy.
CNS Neurol Disord Drug Targets. 2009 Aug;8(4):296-308. [PMID: 19689311]
Christie MA, McKenna JT, Connolly 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.
J Sleep Res. 2008 Dec; 17(4):376-84. [PMID: 19021853]
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 Oct 1; 31(10):1393-8. [PMID: 18853936]
McKenna JT, Cordeira JW, Christie MA, 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. J Sleep Res. 2008 Sep 13. [PMID: 18823428]
Brown RE, McKenna JT, Winston S, Basheer R, Yanagawa Y, Thakkar MM, McCarley RW. Characterization of GABAergic neurons in rapid-eye-movement sleep controlling regions of the brainstem reticular formation in GAD67-green fluorescent protein knock-in mice. Eur J Neurosci. 2008 Jan; 27(2):352-63. [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 Jun 8; 146(4):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 Jan 1; 30(1):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 Sep 1; 141(3):1101-5. [PMID: 16820265]
Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, McCarley RW, Brown RE, Strecker RE. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci. 2006 May; 23(10):2739-48. [PMID: 16817877]
Strecker RE, Basheer R, McKenna JT, McCarley RW. Another chapter in the adenosine story. Sleep. 2006 Apr 1; 29(4):426-8. [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(3):949-58. [PMID: 16154286]
McKenna JT, Vertes RP. Afferent projections to nucleus reuniens of the thalamus. J Comp Neurol. 2004 Dec 6; 480(2):115-42. [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 Res Bull. 2001 Apr; 54(6):619-30.
[PMID: 11403988]
Vertes RP, McKenna JT. Collateral projections from the supramammillary nucleus to the medial septum and hippocampus. Synapse. 2000 Dec 1; 38(3):281-93.
[PMID: 11020231]
Books
Basheer R, McKenna JT, McCarley RW. Encyclopedia of Neuroscience, Squire LR (ed.). Pharmacology of Sleep: Adenosine. 2009; 7:601-610.
Other Publications
McKenna JT. Doctoral dissertation - A Neuroanatomical Investigation of the Median Raphe Nucleus, Supramammillary Nucleus, and Nucleus Reuniens: Possible Implications for the Modulation of the Hippocampal EEG - Vertes RP, advisor. 2001.
Brain Res Bull. 2009 Dec 16;80(6):382-8. Epub 2009 Aug 28. [PMID: 19716862]
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 Res. 2009 Oct 19;1294:128-37. Epub 2009 Jul 28. [PMID: 19643093]
Chen L, Brown RE, McKenna JT, McCarley RW. Animal models of narcolepsy.
CNS Neurol Disord Drug Targets. 2009 Aug;8(4):296-308. [PMID: 19689311]
Christie MA, McKenna JT, Connolly 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.
J Sleep Res. 2008 Dec; 17(4):376-84. [PMID: 19021853]
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 Oct 1; 31(10):1393-8. [PMID: 18853936]
McKenna JT, Cordeira JW, Christie MA, 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. J Sleep Res. 2008 Sep 13. [PMID: 18823428]
Brown RE, McKenna JT, Winston S, Basheer R, Yanagawa Y, Thakkar MM, McCarley RW. Characterization of GABAergic neurons in rapid-eye-movement sleep controlling regions of the brainstem reticular formation in GAD67-green fluorescent protein knock-in mice. Eur J Neurosci. 2008 Jan; 27(2):352-63. [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 Jun 8; 146(4):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 Jan 1; 30(1):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 Sep 1; 141(3):1101-5. [PMID: 16820265]
Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, McCarley RW, Brown RE, Strecker RE. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci. 2006 May; 23(10):2739-48. [PMID: 16817877]
Strecker RE, Basheer R, McKenna JT, McCarley RW. Another chapter in the adenosine story. Sleep. 2006 Apr 1; 29(4):426-8. [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(3):949-58. [PMID: 16154286]
McKenna JT, Vertes RP. Afferent projections to nucleus reuniens of the thalamus. J Comp Neurol. 2004 Dec 6; 480(2):115-42. [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 Res Bull. 2001 Apr; 54(6):619-30.
[PMID: 11403988]
Vertes RP, McKenna JT. Collateral projections from the supramammillary nucleus to the medial septum and hippocampus. Synapse. 2000 Dec 1; 38(3):281-93.
[PMID: 11020231]
Books
Basheer R, McKenna JT, McCarley RW. Encyclopedia of Neuroscience, Squire LR (ed.). Pharmacology of Sleep: Adenosine. 2009; 7:601-610.
Other Publications
McKenna JT. Doctoral dissertation - A Neuroanatomical Investigation of the Median Raphe Nucleus, Supramammillary Nucleus, and Nucleus Reuniens: Possible Implications for the Modulation of the Hippocampal EEG - Vertes RP, advisor. 2001.
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