Division of Sleep Medicine @ Harvard Medical School
Faculty Profile
Robert E. Strecker, PhD
Assistant Professor of Psychiatry, Harvard Medical School
Assistant Professor, Department of Psychiatry, VA Boston Healthcare System
Other Affiliation(s)
Department of Psychology, Stonehill College
Society Memberships
Society for NeuroscienceSleep Research Society
American Association for the Advancement of Science
Research Unit(s)
Director, Section of Behavioral Neuroscience, Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System
Research Interests
Dr. Strecker's research uses animal models to study how the brain controls behavior, especially that of sleep and wakefulness. His early work examined the physiology and neuropharmacology of monoamine neurotransmitter systems in the mammalian brain in relation to sleep, drug abuse, Parkinson's disease, and the potential use of neural transplantation to treat neurological disorders (refs 1-39,42).
Since joining the faculty of Harvard Medical School his work has focused on the brain circuitry involved in the control of REM sleep (refs 41, 43, 44, 50, 55), and non-REM sleep (also known as slow wave sleep; refs 40, 45 - 49, 52 - 54). For example, references 41, 43, and 44 describe brainstem mechanisms controlling REM sleep, in particular the promotion of REM sleep by reticular cholinergic activity and the inhibition of REM sleep by increases in monoaminergic neurotransmission. In the control of non-REM sleep are a unique set of anterior hypothalamic neurons (ventrolateral preoptic area; VLPO) that is selectively activated during non-REM sleep and has been found in all mammals studied to date (ref 51). It was proposed that these neurons are important in the maintenance of non-REM sleep, whereas the inhibition of wakefulness promoting neurotransmitter systems by adenosine is responsible for the sleepiness associated with long periods of wakefulness (ref 40, 47, 52, reviewed in 46).
Cortically projecting and wakefulness promoting cholinergic neurons are found throughout the basal forebrain region, an area that is a potent site for the sleep inducing properties of endogenous adenosine. The cumulative data indicate that adenosine, acting via A1 receptors, inhibits the cortically projecting cholinergic neuronal arousal system found in this basal forebrain region (reviewed in ref 46). These published studies were among those funded by Dr. Strecker's first VA merit award (1999-2004) and this work led directly to his currently funded studies investigating the role of adenosine and the basal forebrain in the pathological sleepiness associated with obstructive sleep apnea (OSA). Thus, in early 2002, Dr. Strecker initiated a new line of research to investigate the behavioral and neurobiological consequences of OSA using a rat model. These projects are now funded by the VA and by NIH/NHLBI.
Currently funded research projects. Despite an understanding of the causes of OSA and the availability of treatment options, the investigation of the consequences/symptoms of OSA remains important because up to 85% of patients with OSA are undiagnosed, spending many years with the disorder. In addition, OSA therapy (e.g., CPAP) does not fully resolve the symptoms in many OSA patients. Thus, the consequences of chronic OSA are an important public health concern that has been little investigated, due, in part, to the relative lack of animal models of OSA. Indeed, recent findings that intermittent hypoxia (IH), by itself, produces cell death in brain regions associated with cognition underscores the importance of studying the consequences of OSA. The primary chararcterisitics of OSA are intermittent hypoxia (IH) and sleep interruption (SI) (fragmentation), and are thought to produce symptoms/signs associated with OSA including excessive daytime sleepiness and various cognitive/attentional impairments. However, it has remained unknown which symptoms/signs of OSA are attributable to SI, and which to IH, because these characteristics are difficult to separate in humans. The overarching hypothesis is that the inhibitory neuromodulator adenosine (AD) mediates the sleepiness associated with OSA. Previous findings by Dr. Strecker supported the hypothesis that AD is a mediator of sleepiness following short (6h) periods of sleep loss, a role in which its inhibitory action on the basal forebrain (BF) wakefulness-promoting neurons appears especially important.
Dr. Strecker developed 2 paradigms in which the OSA characteristics of IH and SI can be separated in the rat, and a third paradigm in which these two conditions are presented simultaneously to best mimic the clinical disorder. A variety of neurobiological and behavioral measures are obtained in these animal models. In the early stages of these projects, Dr. Strecker established collaborations with respiratory physiologists and experts in OSA research (Drs. Liming Ling and David White of HMS, David Gozal of Univ. Louisville, and Maurice Dematteis of Univ. of Grenoble), as well as with behavioral scientists (Drs. Mark Baxter of Oxford University, Jill McGaughy of University of New Hampshire, and Andrea Chiba of UCSD), in order to establish a battery of behavioral tests to fully assess the behavioral and cognitive impairments produced by OSA treatment and sleep loss. Dr. Strecker's lab is now uniquely able to assess the effects of sleep loss, SI, and IH on the following behavioral dimensions: learning and memory, vigilance/attention, motor coordination, executive function, and anxiety/emotion.
Manuscripts are in press or under review that describe the following recently obtained data: 1. Rats exposed to 24h of SI have impaired spatial learning and memory in the water maze task. 24h of SI also blocks hippocampal synaptic plasticity (i.e., long term potentiation) which is necessary for spatial memory formation (Tartar et al., in press Europ. J. Neuroscience). 2. Rats exposed to 24 h of SI are also impaired in a attentioal set shifing, as shown by their an impaired ability to learn new rules in a behavioral test designed to assess executive function (intradimensionl/extradimensional set shifting task, which is analagous to the Wisconsin card sorting test used in human studies). 3. Rats that have undergone as little as 7 h of total sleep deprivation have impaired performance in an operant test of attention (the 5 choice serial reaction time test; Cordova et al., Sleep in press). This task is analagous the psychomotor vigilance test (PVT) used in human studies of sleepiness. 4. SI, but not IH, elevates sleepiness and basal forebrain adenosine levels, supporting out hypothesis that SI is responsible for the excessive daytime sleepiness of OSA and not IH (McKenna et al., submitted to J. Neuroscience).
Since joining the faculty of Harvard Medical School his work has focused on the brain circuitry involved in the control of REM sleep (refs 41, 43, 44, 50, 55), and non-REM sleep (also known as slow wave sleep; refs 40, 45 - 49, 52 - 54). For example, references 41, 43, and 44 describe brainstem mechanisms controlling REM sleep, in particular the promotion of REM sleep by reticular cholinergic activity and the inhibition of REM sleep by increases in monoaminergic neurotransmission. In the control of non-REM sleep are a unique set of anterior hypothalamic neurons (ventrolateral preoptic area; VLPO) that is selectively activated during non-REM sleep and has been found in all mammals studied to date (ref 51). It was proposed that these neurons are important in the maintenance of non-REM sleep, whereas the inhibition of wakefulness promoting neurotransmitter systems by adenosine is responsible for the sleepiness associated with long periods of wakefulness (ref 40, 47, 52, reviewed in 46).
Cortically projecting and wakefulness promoting cholinergic neurons are found throughout the basal forebrain region, an area that is a potent site for the sleep inducing properties of endogenous adenosine. The cumulative data indicate that adenosine, acting via A1 receptors, inhibits the cortically projecting cholinergic neuronal arousal system found in this basal forebrain region (reviewed in ref 46). These published studies were among those funded by Dr. Strecker's first VA merit award (1999-2004) and this work led directly to his currently funded studies investigating the role of adenosine and the basal forebrain in the pathological sleepiness associated with obstructive sleep apnea (OSA). Thus, in early 2002, Dr. Strecker initiated a new line of research to investigate the behavioral and neurobiological consequences of OSA using a rat model. These projects are now funded by the VA and by NIH/NHLBI.
Currently funded research projects. Despite an understanding of the causes of OSA and the availability of treatment options, the investigation of the consequences/symptoms of OSA remains important because up to 85% of patients with OSA are undiagnosed, spending many years with the disorder. In addition, OSA therapy (e.g., CPAP) does not fully resolve the symptoms in many OSA patients. Thus, the consequences of chronic OSA are an important public health concern that has been little investigated, due, in part, to the relative lack of animal models of OSA. Indeed, recent findings that intermittent hypoxia (IH), by itself, produces cell death in brain regions associated with cognition underscores the importance of studying the consequences of OSA. The primary chararcterisitics of OSA are intermittent hypoxia (IH) and sleep interruption (SI) (fragmentation), and are thought to produce symptoms/signs associated with OSA including excessive daytime sleepiness and various cognitive/attentional impairments. However, it has remained unknown which symptoms/signs of OSA are attributable to SI, and which to IH, because these characteristics are difficult to separate in humans. The overarching hypothesis is that the inhibitory neuromodulator adenosine (AD) mediates the sleepiness associated with OSA. Previous findings by Dr. Strecker supported the hypothesis that AD is a mediator of sleepiness following short (6h) periods of sleep loss, a role in which its inhibitory action on the basal forebrain (BF) wakefulness-promoting neurons appears especially important.
Dr. Strecker developed 2 paradigms in which the OSA characteristics of IH and SI can be separated in the rat, and a third paradigm in which these two conditions are presented simultaneously to best mimic the clinical disorder. A variety of neurobiological and behavioral measures are obtained in these animal models. In the early stages of these projects, Dr. Strecker established collaborations with respiratory physiologists and experts in OSA research (Drs. Liming Ling and David White of HMS, David Gozal of Univ. Louisville, and Maurice Dematteis of Univ. of Grenoble), as well as with behavioral scientists (Drs. Mark Baxter of Oxford University, Jill McGaughy of University of New Hampshire, and Andrea Chiba of UCSD), in order to establish a battery of behavioral tests to fully assess the behavioral and cognitive impairments produced by OSA treatment and sleep loss. Dr. Strecker's lab is now uniquely able to assess the effects of sleep loss, SI, and IH on the following behavioral dimensions: learning and memory, vigilance/attention, motor coordination, executive function, and anxiety/emotion.
Manuscripts are in press or under review that describe the following recently obtained data: 1. Rats exposed to 24h of SI have impaired spatial learning and memory in the water maze task. 24h of SI also blocks hippocampal synaptic plasticity (i.e., long term potentiation) which is necessary for spatial memory formation (Tartar et al., in press Europ. J. Neuroscience). 2. Rats exposed to 24 h of SI are also impaired in a attentioal set shifing, as shown by their an impaired ability to learn new rules in a behavioral test designed to assess executive function (intradimensionl/extradimensional set shifting task, which is analagous to the Wisconsin card sorting test used in human studies). 3. Rats that have undergone as little as 7 h of total sleep deprivation have impaired performance in an operant test of attention (the 5 choice serial reaction time test; Cordova et al., Sleep in press). This task is analagous the psychomotor vigilance test (PVT) used in human studies of sleepiness. 4. SI, but not IH, elevates sleepiness and basal forebrain adenosine levels, supporting out hypothesis that SI is responsible for the excessive daytime sleepiness of OSA and not IH (McKenna et al., submitted to J. Neuroscience).
Trainees
Alvhild Alette Bjorkum, PhD, 1995-1997
James Timothy McKenna, PhD, 2001-present
Christopher Peyton Ward, PhD, 2003-present
Jaime Tartar, PhD, 2004-present
John McCoy, PhD, 2004-present
Michael Christie, PhD, 2005-present
James Timothy McKenna, PhD, 2001-present
Christopher Peyton Ward, PhD, 2003-present
Jaime Tartar, PhD, 2004-present
John McCoy, PhD, 2004-present
Michael Christie, PhD, 2005-present
Mentor(s)
Research Funding
Currently Active Grants with Strecker as PI or investigator, and summary of research area in italics.
2004-2009 Veterans Administration Merit Review (R01 equivalent in VA) PI
Adenosine and the Basal Forebrain in the Control of Behavioral State
Rat model of obstructive sleep apnea using concurrent exposure to intermittent hypoxia and sleep interruption.
2003-2008 NHLB (2 P50 HLO60292; David White = PI)
Harvard Center on Sleep Neurobiology and Sleep Apnea
Core C: Behavioral Core PI
Behavioral tests in rodents assessing vigilance/attention, learning and memory, motor perfromance, emotion & anxiety, executive function.
Project 2: Behavioral & Neurobiological Consequences of Obstructive Sleep Apnea (McCarley = PI) co-PI
Comparison of intermittent hypoxia and sleep interruption in the etiology of the symptoms of obstructive sleep apnea. Animal models.
Project 4:
(Clif Saper = PI) investigator
2002-2007 NIH/NIMH (R37 MH39683; McCarley = PI) Investigator
Synaptic Basis of Sleep Cycle Control (MERIT Award, renewed over 20yr)
Cholinergic and adenosinergic mechanisms of sleep. Animal models
2004-2009 Veterans Administration Merit Review (R01 equivalent in VA) PI
Adenosine and the Basal Forebrain in the Control of Behavioral State
Rat model of obstructive sleep apnea using concurrent exposure to intermittent hypoxia and sleep interruption.
2003-2008 NHLB (2 P50 HLO60292; David White = PI)
Harvard Center on Sleep Neurobiology and Sleep Apnea
Core C: Behavioral Core PI
Behavioral tests in rodents assessing vigilance/attention, learning and memory, motor perfromance, emotion & anxiety, executive function.
Project 2: Behavioral & Neurobiological Consequences of Obstructive Sleep Apnea (McCarley = PI) co-PI
Comparison of intermittent hypoxia and sleep interruption in the etiology of the symptoms of obstructive sleep apnea. Animal models.
Project 4:
(Clif Saper = PI) investigator
2002-2007 NIH/NIMH (R37 MH39683; McCarley = PI) Investigator
Synaptic Basis of Sleep Cycle Control (MERIT Award, renewed over 20yr)
Cholinergic and adenosinergic mechanisms of sleep. Animal models
Teaching
Harvard Medical School Graduate School courses
1995- Neuroscience Basics of Pyschopharmacology , Invited Lecturer
2002 Led a 3 day workshop on "Sleep and Depression" at the Sleep Workshop of the Multi-site Training Program for Basic Sleep Research, held in Lake Arrowhead, California, (PI = Dr. Michael Chase), entitled "Interactions and Intersections between Sleep and Other Disciplines".
Teaching leadership:
2005- Creator/director of PC343, Research in Biopsychology, a research internship program, for undergraduates at Stonehill College, including a 1h/wk research seminar. Enrollment ~6 students/semester.
1995- Neuroscience Basics of Pyschopharmacology , Invited Lecturer
2002 Led a 3 day workshop on "Sleep and Depression" at the Sleep Workshop of the Multi-site Training Program for Basic Sleep Research, held in Lake Arrowhead, California, (PI = Dr. Michael Chase), entitled "Interactions and Intersections between Sleep and Other Disciplines".
Teaching leadership:
2005- Creator/director of PC343, Research in Biopsychology, a research internship program, for undergraduates at Stonehill College, including a 1h/wk research seminar. Enrollment ~6 students/semester.
Selected Publications
Koob GF, Strecker RE, Bloom FE. Effects of naloxone on the anticonflict properties of alcohol and chlordiazepoxide.
Substance and Alcohol Actions/Misuse. 1980; 1: 447-457.
Joyce EM, Koob GF, Strecker RE, Iversen SD. The behavioral effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus.
Brain Res. 1981; 221: 359-370.
Strecker RE, Roberts DCS, Koob GF. Apomorphine-induced facilitation of intracranial self-stimulation following dopamine denervation of the nucleus accumbens.
Pharmac. Biochem. Behav. 1982; 17: 1015-1018.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Behavioral correlates of dopaminergic unit activity in freely moving cats.
Brain Res. 1983; 258: 217-228.
Strecker RE, Steinfels GF, Jacobs BL. Dopaminergic unit activity in freely moving cats: lack of relationship to feeding, satiety and glucose injections.
Brain Res. 1983; 260: 317-321.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Response of dopaminergic neurons in cat to auditory stimuli presented across the sleep-waking cycle.
Brain Res. 1983; 227: 150-154.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Raphe unit activity in freely moving cats is altered by manipulations of central but not peripheral motor systems.
Brain Res. 1983; 279: 77-84.
Strecker RE, Steinfels GF, Abercrombie ED, Jacobs BL. Caudate unit activity in freely moving cats: effects of phasic auditory and visual stimuli.
Brain Res. 1985; 329: 350-353.
Strecker RE, Jacobs BL. Nigral dopaminergic unit activity in behaving cats: effects of arousal on spontaneous discharge and sensory evoked activity.
Brain Res. 1985; 361: 339-350.
Rasmussen K, Strecker RE, Jacobs BL. Single unit response of noradrenergic, serotonergic and dopaminergic neurons in freely moving cats to simple sensory stimuli.
Brain Res. 1986; 369:336-340.
Brundin P, Nilsson OG, Strecker RE, Lindvall O, Åstedt B, Björklund A. Behavioral effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease.
Exp.Brain Res. 1986; 65: 235-240.
Strecker RE, Sharp T, Brundin P, Zetterström T, Ungerstedt U, Björklund A. Autoregulation of dopamine release and metabolism by intrastriatal nigral grafts as revealed by intracerebral dialysis.
Neurosci. 1987; 22: 169-178.
Brundin P, Strecker RE, Londos E, Björklund A. Dopamine neurons grafted unilaterally to the nucleus accumbens affect drug-induced circling and locomotion.
Exp. Brain Res. 1987; 69: 183-194.
Brundin P, Strecker RE, Widner H, Clarke DJ, Nilsson OG, Åstedt B, Lindvall O, Björklund A. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behavior, and dopamine release.
Exp. Brain Res. 1988; 70: 192-208.
Brundin P, Barbin G, Strecker RE, Isacson O, Prochiantz A, Björklund A. Survival and function of dissociated rat dopamine neurones grafted at different developmental stages or after being cultured in vitro.
Devel. Brain Res. 1988; 39: 233-243.
Nilsson OG, Strecker RE, Daszuta A, Björklund A. Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in spatial learning in the rat.
Brain Res. 1988; 453: 235-246.
Nilsson OG, Brundin P, Widner H, Strecker RE, Björklund A. Human fetal basal forebrain neurons grafted to the denervated rat hippocampus produce an organotypic cholinergic reinnervation pattern.
Brain Res. 1988; 456: 193-198.
Kalén P, Strecker RE, Rosengren E, Björklund A. Endogenous release of neuronal serotonin and 5-HIAA in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high performance liquid chromatography with fluorimetric detection.
J. Neurochem. 1988; 51: 1422-1435.
Clarke DJ, Brundin P, Strecker RE, Nilsson OG, Björklund A, Lindvall O. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry.
Exp. Brain Res. 1988; 73: 115-126.
Daszuta A, Strecker RE, Brundin P, Björklund A. Serotonin neurons grafted to the adult rat hippocampus: I. Time course of growth as studied by immunohistochemistry and biochemistry.
Brain Res. 1988; 458:1-19.
Daszuta A, Kalén P, Strecker RE, Björklund A. Serotonin neurons grafted to the adult rat hippocampus. II. 5-HT release as studied by intracerebral microdialysis.
Brain Res. 1989; 498: 323-332.
Brundin P, Widner H, Nilsson OG, Strecker RE, Björklund A. Intracerebral xenografts of dopamine neurons: the role of immunosuppression and the blood-brain barrier.
Exp. Brain Res. 1989; 75: 195-207.
Forni C, Brundin P, Strecker RE, El Ganouni S, Björklund A, Nieoullon A. Time-course of recovery of dopamine neuron activity during reinnervation of the denervated striatum by fetal mesencephalic grafts as assessed by in vivo voltammetry.
Exp. Brain Res. 1989; 76: 75-87.
Kalén P, Strecker RE, Rosengren E, Björklund A. Regulation of striatal serotonin release by the lateral habenula-dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and gaba.
Brain Res. 1989; 492: 187-202.
Strecker RE, Miao R, Loring JF. Survival and function of aggregate cultures of rat fetal dopamine neurons grafted in a rat model of Parkinson's disease.
Exp. Brain Res. 1989; 76: 315-322.
Huffaker TK, Boss BD, Morgan AS, Neff NT, Strecker RE, Spence MS, Miao R. Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease.
Exp. Brain Res. 1989; 77: 329-336.
Doucet G, Brundin P, Seth S, Murata Y, Strecker RE, Triarhou L, Ghetti B, Björklund A. Degeneration and graft-induced restoration of dopamine innervation in the weaver mouse neostriatum: a quantitative radioautographic study of [3H]dopamine uptake.
Exp. Brain Res. 1989; 77: 552-568.
Freeman TB, Spence MS, Boss BD, Spector DH, Strecker RE, Olanow CW, Kordower JH. Development of dopaminergic neurons in the human substantia nigra.
Exp Neurology. 1991; 113: 344-353.
La Gamma EF, Weisinger G, Lenn NJ, Strecker RE. Genetically modified striatal astrocytes grafted to the brain: pharmacological control of an inducible promoter.
J. Neural Transplantation Plasticity. 1992; 3: 244-245.
Basso MA, Strecker RE, Evinger C. Midbrain 6-hydroxydopamine lesions modulate blink reflex excitability.
Exp. Brain Res. 1993; 94: 88-96.
LaGamma EF, Weisinger G, Lenn NJ, Strecker RE. Genetically modified primary astrocytes as cellular vehicles for gene tharapy in the brain.
Cell Transplantation. 1993; 2: 207-214.
McNeish CS, Svingos AL, Hitzemann R, Strecker RE. The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens.
Pharmacol. Biochem. Beh. 1993; 45: 759-763.
Spector DH, Boss BD, Strecker RE. A model three-dimensional culture system for mammalian dopaminergic precursor cells: application for functional intracerebral transplantation.
Exp. Neurology. 1993; 124: 253-264.
Strecker RE, Moneta ME. Electrical stimulation of the kindled hippocampus briefly increases extracellular dopamine in the nucleus accumbens.
Neurosci. Lett. 1994; 176: 173-177.
La Gamma EF, Strecker RE, Lenn NJ, DeCristofaro JD, Weisinger G. Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo.
Exp. Neurol. 1994; 130: 304-310.
Strecker RE, Eberle WF, Ashby Jr CR. Extracellular dopamine and its metabolites in the nucleus accumbens of Fischer and Lewis rats: Basal levels and cocaine-induced changes.
Life Sciences. 1995; 56: PL135-PL141.
Liu X, Strecker RE, Brener JM. Low doses of apomorphine suppress operant motor performance in rats.
Pharmacol. Biochem. Beh. 1995; 53: 335-340.
Clark RN, Ashby Jr CR, Ramachandran C, Dewey SL, Strecker RE. Effect of acute and chronic fluoxetine on extracellular dopamine levels in the caudate-putamen and nucleus accumbens.
Synapse. 1996; 23: 125-131.
Kurata K, Ashby Jr CR, Oberlender R, Tanii Y, Kurachi M, Rini NJ, Strecker RE. The characterization of the effect of locally applied N-methylquipazine, a 5-HT3 receptor agonist, on extracellular dopamine levels in the anterior medial prefrontal cortex in the rat: An in vivo microdialysis study.
Synapse. 1996; 24: 313-321.
Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjørkum AA, Greene RW, McCarley RW. Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness.
Science. 1997; 276: 1265-1268.
Thakkar MM, Strecker RE, McCarley RW. Behavioral state control through differential serotonergic inhibition in the mesopontine cholinergic nuclei: A simultaneous unit recording and microdialysis study.
J. Neurosci. 1998; 18: 5490-5497.
Liu X, Strecker RE, Brener J. A comparison of the effects of amphetamine and low doses of apomorphine on operant force production, inter-response times and response duration in rat.
Psychopharmacology. 1999; 145: 351-359.
Strecker RE, Thakkar MM, Porkka-Heiskanen T, Dauphin LJ, Bjørkum AA, McCarley RW. Behavioral state-related changes of extracellular serotonin concentration in the pedunculopontine tegmental nucleus: a microdialysis study in freely moving animals.
Sleep Research Online. 1999; 2: 21-27. http://www.sro.org/1999/strecker/21/
Thakkar MM, Ramesh V, Cape EG, Winston S, Strecker RE, McCarley RW. REM Sleep enhancement and behavioral cataplexy following orexin (hypocretin)-ii receptor antisense perfusion in the pontine reticular formation.
Sleep Research Online. 1999; 2: 113-120.
Basheer R, Porkka-Heiskanen T, Strecker RE, Thakkar MM, McCarley RW. Adenosine as a biological signal mediating sleepiness following prolonged wakefulness.
Biological Signals and Receptors. 2000; 9: 319-327.
Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Portas CM, Greene RW, McCarley RW. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state.
Behavioural Brain Research. 2000; 115: 183-204. http://www.elsevier.nl/inca/publications/store/5/0/6/0/4/5/
Porkka-Heiskanen T, Strecker RE, McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study.
Neuroscience. 2000; 99: 507-517.
Thakkar MM, Ramesh V, Strecker RE, McCarley RW. Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats.
Arch. Ital. Biol. 2001; 139: 313-328
Strecker RE, Nalwalk J, Dauphin LJ, Thakkar MM, Chen Y, Ramesh V, Hough LB, McCarley RW. Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: An in vivo microdialysis study.
Neuroscience. 2002; 113: 663-670.
Thakkar M, Strecker RE, McCarley RW. Phasic but not tonic REM selective discharge of periaqueductal gray neurons in freely behaving animals: Relevance to postulates of GABAergic inhibition of monoaminergic neurons.
Brain Res. 2002; 945: 276-80.
Gaus SE, Strecker RE, Tate BA, Parker RA, Saper CB. Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species.
Neuroscience. 2002; 115: 285-294.
Thakkar MM, Delgiacco RA, Strecker RE, McCarley RW. Adenosinergic inhibition of basal forebrain wakefulness - active neurons: A simultaneous unit recording and microdialysis study in freely behaving cats.
Neuroscience. 2003; 122: 1107-1113.
McKenna JT, Dauphin, LJ, Mulkern KJ, Stronge AM, McCarley RW, Strecker RE. Nocturnal elevation of extracellular adenosine in the rat basal forebrain.
Sleep Research Online. 2003; 5: 155-160.
Bjorkum AA, Strecker RE, Portas CM, Porkka-Heiskanen T, Thakkar M, McCarley RW. Perfusion of a 5-HT1A antagonist in the cat DRN increases wakefulness and extracellular 5-HT level in DRN.
Sleep Research Online. 2003; 5: 149-154.
Ramesh V, Thakkar MM, Strecker RE, Basheer R, McCarley RW. Wakefulness-inducing effects of histamine in the basal forebrain of freely moving rats.
Behav Brain Res 2004; 152:271-278.
Lo CC, Chou T, Penzel T, Scammell TE, Strecker RE, Stanley HE, Ivanov PCh.
Common scale-invariant patterns of sleep-wake transitions across mammalian species.
Proc Natl Acad Sci U S A. 2004; 101: 17545-17548.
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.
Córdova CA, Said BO, McCarley RW, Baxter MG, Chiba AA, Strecker RE. Sleep deprivation in rats produces attentional impairments on a 5-Choice serial reaction time task.
Sleep. 2006; 29:69-76.
Tartar JL, Ward CP, McKenna JT, Thakkar MM, Arrigoni E, McCarley RW, Brown RE, and Strecker RE. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.
In press, Europ. J. Neurosci., 2006.
Substance and Alcohol Actions/Misuse. 1980; 1: 447-457.
Joyce EM, Koob GF, Strecker RE, Iversen SD. The behavioral effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus.
Brain Res. 1981; 221: 359-370.
Strecker RE, Roberts DCS, Koob GF. Apomorphine-induced facilitation of intracranial self-stimulation following dopamine denervation of the nucleus accumbens.
Pharmac. Biochem. Behav. 1982; 17: 1015-1018.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Behavioral correlates of dopaminergic unit activity in freely moving cats.
Brain Res. 1983; 258: 217-228.
Strecker RE, Steinfels GF, Jacobs BL. Dopaminergic unit activity in freely moving cats: lack of relationship to feeding, satiety and glucose injections.
Brain Res. 1983; 260: 317-321.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Response of dopaminergic neurons in cat to auditory stimuli presented across the sleep-waking cycle.
Brain Res. 1983; 227: 150-154.
Steinfels GF, Heym J, Strecker RE, Jacobs BL. Raphe unit activity in freely moving cats is altered by manipulations of central but not peripheral motor systems.
Brain Res. 1983; 279: 77-84.
Strecker RE, Steinfels GF, Abercrombie ED, Jacobs BL. Caudate unit activity in freely moving cats: effects of phasic auditory and visual stimuli.
Brain Res. 1985; 329: 350-353.
Strecker RE, Jacobs BL. Nigral dopaminergic unit activity in behaving cats: effects of arousal on spontaneous discharge and sensory evoked activity.
Brain Res. 1985; 361: 339-350.
Rasmussen K, Strecker RE, Jacobs BL. Single unit response of noradrenergic, serotonergic and dopaminergic neurons in freely moving cats to simple sensory stimuli.
Brain Res. 1986; 369:336-340.
Brundin P, Nilsson OG, Strecker RE, Lindvall O, Åstedt B, Björklund A. Behavioral effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease.
Exp.Brain Res. 1986; 65: 235-240.
Strecker RE, Sharp T, Brundin P, Zetterström T, Ungerstedt U, Björklund A. Autoregulation of dopamine release and metabolism by intrastriatal nigral grafts as revealed by intracerebral dialysis.
Neurosci. 1987; 22: 169-178.
Brundin P, Strecker RE, Londos E, Björklund A. Dopamine neurons grafted unilaterally to the nucleus accumbens affect drug-induced circling and locomotion.
Exp. Brain Res. 1987; 69: 183-194.
Brundin P, Strecker RE, Widner H, Clarke DJ, Nilsson OG, Åstedt B, Lindvall O, Björklund A. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behavior, and dopamine release.
Exp. Brain Res. 1988; 70: 192-208.
Brundin P, Barbin G, Strecker RE, Isacson O, Prochiantz A, Björklund A. Survival and function of dissociated rat dopamine neurones grafted at different developmental stages or after being cultured in vitro.
Devel. Brain Res. 1988; 39: 233-243.
Nilsson OG, Strecker RE, Daszuta A, Björklund A. Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in spatial learning in the rat.
Brain Res. 1988; 453: 235-246.
Nilsson OG, Brundin P, Widner H, Strecker RE, Björklund A. Human fetal basal forebrain neurons grafted to the denervated rat hippocampus produce an organotypic cholinergic reinnervation pattern.
Brain Res. 1988; 456: 193-198.
Kalén P, Strecker RE, Rosengren E, Björklund A. Endogenous release of neuronal serotonin and 5-HIAA in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high performance liquid chromatography with fluorimetric detection.
J. Neurochem. 1988; 51: 1422-1435.
Clarke DJ, Brundin P, Strecker RE, Nilsson OG, Björklund A, Lindvall O. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry.
Exp. Brain Res. 1988; 73: 115-126.
Daszuta A, Strecker RE, Brundin P, Björklund A. Serotonin neurons grafted to the adult rat hippocampus: I. Time course of growth as studied by immunohistochemistry and biochemistry.
Brain Res. 1988; 458:1-19.
Daszuta A, Kalén P, Strecker RE, Björklund A. Serotonin neurons grafted to the adult rat hippocampus. II. 5-HT release as studied by intracerebral microdialysis.
Brain Res. 1989; 498: 323-332.
Brundin P, Widner H, Nilsson OG, Strecker RE, Björklund A. Intracerebral xenografts of dopamine neurons: the role of immunosuppression and the blood-brain barrier.
Exp. Brain Res. 1989; 75: 195-207.
Forni C, Brundin P, Strecker RE, El Ganouni S, Björklund A, Nieoullon A. Time-course of recovery of dopamine neuron activity during reinnervation of the denervated striatum by fetal mesencephalic grafts as assessed by in vivo voltammetry.
Exp. Brain Res. 1989; 76: 75-87.
Kalén P, Strecker RE, Rosengren E, Björklund A. Regulation of striatal serotonin release by the lateral habenula-dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and gaba.
Brain Res. 1989; 492: 187-202.
Strecker RE, Miao R, Loring JF. Survival and function of aggregate cultures of rat fetal dopamine neurons grafted in a rat model of Parkinson's disease.
Exp. Brain Res. 1989; 76: 315-322.
Huffaker TK, Boss BD, Morgan AS, Neff NT, Strecker RE, Spence MS, Miao R. Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease.
Exp. Brain Res. 1989; 77: 329-336.
Doucet G, Brundin P, Seth S, Murata Y, Strecker RE, Triarhou L, Ghetti B, Björklund A. Degeneration and graft-induced restoration of dopamine innervation in the weaver mouse neostriatum: a quantitative radioautographic study of [3H]dopamine uptake.
Exp. Brain Res. 1989; 77: 552-568.
Freeman TB, Spence MS, Boss BD, Spector DH, Strecker RE, Olanow CW, Kordower JH. Development of dopaminergic neurons in the human substantia nigra.
Exp Neurology. 1991; 113: 344-353.
La Gamma EF, Weisinger G, Lenn NJ, Strecker RE. Genetically modified striatal astrocytes grafted to the brain: pharmacological control of an inducible promoter.
J. Neural Transplantation Plasticity. 1992; 3: 244-245.
Basso MA, Strecker RE, Evinger C. Midbrain 6-hydroxydopamine lesions modulate blink reflex excitability.
Exp. Brain Res. 1993; 94: 88-96.
LaGamma EF, Weisinger G, Lenn NJ, Strecker RE. Genetically modified primary astrocytes as cellular vehicles for gene tharapy in the brain.
Cell Transplantation. 1993; 2: 207-214.
McNeish CS, Svingos AL, Hitzemann R, Strecker RE. The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens.
Pharmacol. Biochem. Beh. 1993; 45: 759-763.
Spector DH, Boss BD, Strecker RE. A model three-dimensional culture system for mammalian dopaminergic precursor cells: application for functional intracerebral transplantation.
Exp. Neurology. 1993; 124: 253-264.
Strecker RE, Moneta ME. Electrical stimulation of the kindled hippocampus briefly increases extracellular dopamine in the nucleus accumbens.
Neurosci. Lett. 1994; 176: 173-177.
La Gamma EF, Strecker RE, Lenn NJ, DeCristofaro JD, Weisinger G. Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo.
Exp. Neurol. 1994; 130: 304-310.
Strecker RE, Eberle WF, Ashby Jr CR. Extracellular dopamine and its metabolites in the nucleus accumbens of Fischer and Lewis rats: Basal levels and cocaine-induced changes.
Life Sciences. 1995; 56: PL135-PL141.
Liu X, Strecker RE, Brener JM. Low doses of apomorphine suppress operant motor performance in rats.
Pharmacol. Biochem. Beh. 1995; 53: 335-340.
Clark RN, Ashby Jr CR, Ramachandran C, Dewey SL, Strecker RE. Effect of acute and chronic fluoxetine on extracellular dopamine levels in the caudate-putamen and nucleus accumbens.
Synapse. 1996; 23: 125-131.
Kurata K, Ashby Jr CR, Oberlender R, Tanii Y, Kurachi M, Rini NJ, Strecker RE. The characterization of the effect of locally applied N-methylquipazine, a 5-HT3 receptor agonist, on extracellular dopamine levels in the anterior medial prefrontal cortex in the rat: An in vivo microdialysis study.
Synapse. 1996; 24: 313-321.
Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjørkum AA, Greene RW, McCarley RW. Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness.
Science. 1997; 276: 1265-1268.
Thakkar MM, Strecker RE, McCarley RW. Behavioral state control through differential serotonergic inhibition in the mesopontine cholinergic nuclei: A simultaneous unit recording and microdialysis study.
J. Neurosci. 1998; 18: 5490-5497.
Liu X, Strecker RE, Brener J. A comparison of the effects of amphetamine and low doses of apomorphine on operant force production, inter-response times and response duration in rat.
Psychopharmacology. 1999; 145: 351-359.
Strecker RE, Thakkar MM, Porkka-Heiskanen T, Dauphin LJ, Bjørkum AA, McCarley RW. Behavioral state-related changes of extracellular serotonin concentration in the pedunculopontine tegmental nucleus: a microdialysis study in freely moving animals.
Sleep Research Online. 1999; 2: 21-27. http://www.sro.org/1999/strecker/21/
Thakkar MM, Ramesh V, Cape EG, Winston S, Strecker RE, McCarley RW. REM Sleep enhancement and behavioral cataplexy following orexin (hypocretin)-ii receptor antisense perfusion in the pontine reticular formation.
Sleep Research Online. 1999; 2: 113-120.
Basheer R, Porkka-Heiskanen T, Strecker RE, Thakkar MM, McCarley RW. Adenosine as a biological signal mediating sleepiness following prolonged wakefulness.
Biological Signals and Receptors. 2000; 9: 319-327.
Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Portas CM, Greene RW, McCarley RW. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state.
Behavioural Brain Research. 2000; 115: 183-204. http://www.elsevier.nl/inca/publications/store/5/0/6/0/4/5/
Porkka-Heiskanen T, Strecker RE, McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study.
Neuroscience. 2000; 99: 507-517.
Thakkar MM, Ramesh V, Strecker RE, McCarley RW. Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats.
Arch. Ital. Biol. 2001; 139: 313-328
Strecker RE, Nalwalk J, Dauphin LJ, Thakkar MM, Chen Y, Ramesh V, Hough LB, McCarley RW. Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: An in vivo microdialysis study.
Neuroscience. 2002; 113: 663-670.
Thakkar M, Strecker RE, McCarley RW. Phasic but not tonic REM selective discharge of periaqueductal gray neurons in freely behaving animals: Relevance to postulates of GABAergic inhibition of monoaminergic neurons.
Brain Res. 2002; 945: 276-80.
Gaus SE, Strecker RE, Tate BA, Parker RA, Saper CB. Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species.
Neuroscience. 2002; 115: 285-294.
Thakkar MM, Delgiacco RA, Strecker RE, McCarley RW. Adenosinergic inhibition of basal forebrain wakefulness - active neurons: A simultaneous unit recording and microdialysis study in freely behaving cats.
Neuroscience. 2003; 122: 1107-1113.
McKenna JT, Dauphin, LJ, Mulkern KJ, Stronge AM, McCarley RW, Strecker RE. Nocturnal elevation of extracellular adenosine in the rat basal forebrain.
Sleep Research Online. 2003; 5: 155-160.
Bjorkum AA, Strecker RE, Portas CM, Porkka-Heiskanen T, Thakkar M, McCarley RW. Perfusion of a 5-HT1A antagonist in the cat DRN increases wakefulness and extracellular 5-HT level in DRN.
Sleep Research Online. 2003; 5: 149-154.
Ramesh V, Thakkar MM, Strecker RE, Basheer R, McCarley RW. Wakefulness-inducing effects of histamine in the basal forebrain of freely moving rats.
Behav Brain Res 2004; 152:271-278.
Lo CC, Chou T, Penzel T, Scammell TE, Strecker RE, Stanley HE, Ivanov PCh.
Common scale-invariant patterns of sleep-wake transitions across mammalian species.
Proc Natl Acad Sci U S A. 2004; 101: 17545-17548.
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.
Córdova CA, Said BO, McCarley RW, Baxter MG, Chiba AA, Strecker RE. Sleep deprivation in rats produces attentional impairments on a 5-Choice serial reaction time task.
Sleep. 2006; 29:69-76.
Tartar JL, Ward CP, McKenna JT, Thakkar MM, Arrigoni E, McCarley RW, Brown RE, and Strecker RE. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.
In press, Europ. J. Neurosci., 2006.
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