Division of Sleep Medicine @ Harvard Medical School
Faculty Profile
Ritchie Edward Brown, PhD
Assistant Professor of Psychiatry, Harvard Medical School
Assistant Professor, Department of Psychiatry, VA Boston Healthcare System
Address
VAMC Brockton, Laboratory of Neuroscience940 Belmont St. Research 151-C
Brockton, MA 02301
USA
Email ritchie_brown@hms.harvard.edu
Society Memberships
Sleep Research SocietySociety for Neuroscience
Research Unit(s)
Head of the in vitro neurophysiology section of the Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System
Research Interests
The changes in brain physiology which occur over the course of the sleep-wake cycle are controlled by a small number of neurotransmitter systems located in the basal forebrain, hypothalamus, midbrain and brainstem. These neurotransmitter systems precisely regulate each other as well as the function of the rest of the brain through diffuse and widespread projections. As well as explaining how the sleep-wake cycle operates, investigation of these systems gives insight into mechanisms controlling consciousness, emotion and autonomic function. Drugs which modulate the function of these neurotransmitter systems are widely used for the treatment of many major neurological and psychiatric conditions such as clinical depression and schizophrenia.
The focus of this investigator's research program has been to characterize the interactions between these systems and their effects in target regions using in vitro electrophysiological techniques in combination with anatomical and molecular biological methods. Two neurotransmitter systems located in the posterior hypothalamus, the histamine and orexin/hypocretin systems have been the focus of our attention. The central histamine system contributes to maintenance of the waking state and antagonism of histamine H1 receptors is the main mechanism by which classical antihistamines used in the treatment of allergy cause sedation. The orexin/hypocretin system has generated great interest due to its involvement in the pathogenesis of the disease, narcolepsy and more recently has been implicated in drug addiction. We are currently studying the effects of orexins on brainstem neurons involved in controlling rapid-eye-movement sleep.
The focus of this investigator's research program has been to characterize the interactions between these systems and their effects in target regions using in vitro electrophysiological techniques in combination with anatomical and molecular biological methods. Two neurotransmitter systems located in the posterior hypothalamus, the histamine and orexin/hypocretin systems have been the focus of our attention. The central histamine system contributes to maintenance of the waking state and antagonism of histamine H1 receptors is the main mechanism by which classical antihistamines used in the treatment of allergy cause sedation. The orexin/hypocretin system has generated great interest due to its involvement in the pathogenesis of the disease, narcolepsy and more recently has been implicated in drug addiction. We are currently studying the effects of orexins on brainstem neurons involved in controlling rapid-eye-movement sleep.
Trainees
Tatiana Korotkova 2000-2002; Jaime L. Tartar, PhD 2004-present
Mentor(s)
Research Funding
Investigator on NIMH R01 MH62522 (Robert McCarley PI) "Orexin and the control of sleep and wakefulness".
Selected Publications
Korotkova TM, Ponomarenko AA, Brown RE, Haas HL. Functional diversity of ventral midbrain dopamine and ABAergic neurons.
Mol Neurobiol. 2004 Jun;29(3):243-59. Review. [PMID: 15181237]
Selbach O, Doreulee N, Bohla C, Eriksson KS, Sergeeva OA, Poelchen W, Brown RE, Haas HL. Orexins/hypocretins cause sharp wave- and theta-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling. Neuroscience. 2004;127(2):519-28. [PMID: 15262340]
Sergeeva OA, Korotkova TM, Scherer A, Brown RE, Haas HL. Co-expression of non-selective cation channels of the transient receptor potential canonical family in central aminergic neurones.
J Neurochem. 2003 Jun;85(6):1547-52. [PMID: 12787073]
Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins.
J Neurosci. 2003 Jan 1;23(1):7-11. [PMID: 12514194]
Brown RE, Sergeeva OA, Eriksson KS, Haas HL. Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline).
J Neurosci. 2002 Oct 15;22(20):8850-9. [PMID: 12388591]
Korotkova TM, Eriksson KS, Haas HL, Brown RE. Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro.
Regul Pept. 2002 Mar 15;104(1-3):83-9. [PMID: 11830281]
Korotkova TM, Haas HL, Brown RE. Histamine excites GABAergic cells in the rat substantia nigra and ventral
tegmental area in vitro.
Neurosci Lett. 2002 Mar 8;320(3):133-6. [PMID: 11852180]
Eriksson KS, Sergeeva O, Brown RE, Haas HL. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus.
J Neurosci. 2001 Dec 1;21(23):9273-9. [PMID: 11717361]
Stevens DR, Eriksson KS, Brown RE, Haas HL. The mechanism of spontaneous firing in histamine neurons.
Behav Brain Res. 2001 Oct 15;124(2):105-12. Review. [PMID: 11640962]
Doreulee N, Brown RE, Yanovsky Y, Godecke A, Schrader J, Haas HL. Defective hippocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice.
Synapse. 2001 Sep 1;41(3):191-4. [PMID: 11391779]
Brown RE, Stevens DR, Haas HL. The physiology of brain histamine.
Prog Neurobiol. 2001 Apr;63(6):637-72. Review. [PMID: 11164999]
Brown RE, Sergeeva O, Eriksson KS, Haas HL. Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat.
Neuropharmacology. 2001 Mar;40(3):457-9. [PMID: 11166339]
Doreulee N, Yanovsky Y, Flagmeyer I, Stevens DR, Haas HL, Brown RE. Histamine H(3) receptors depress synaptic transmission in the corticostriatal pathway.
Neuropharmacology. 2001;40(1):106-13. [PMID: 11077076]
Brown RE, Haas HL. On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus.
J Physiol. 1999 Mar 15;515 ( Pt 3):777-86. [PMID: 10066904]
Wilson RI, Godecke A, Brown RE, Schrader J, Haas HL. Mice deficient in endothelial nitric oxide synthase exhibit a selective deficit in hippocampal long-term potentiation.
Neuroscience. 1999;90(4):1157-65. [PMID: 10338286]
Manahan-Vaughan D, Reymann KG, Brown RE. In vivo electrophysiological investigations into the role of histamine in the dentate gyrus of the rat.
Neuroscience. 1998 Jun;84(3):783-90. [PMID: 9579783]
Selbach O, Brown RE, Haas HL. Long-term increase of hippocampal excitability by histamine and cyclic AMP.
Neuropharmacology. 1997 Nov-Dec;36(11-12):1539-48. [PMID: 9517424]
Fedorov NB, Brown RE, Reymann KG. Fast increases of AMPA receptor sensitivity following tetanus-induced
potentiation in the CA1 region of the rat hippocampus.
Neuroreport. 1997 Jan 20;8(2):411-4. [PMID: 9080418]
Brown RE, Reymann KG. Histamine H3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro.
J Physiol. 1996 Oct 1;496 ( Pt 1):175-84. [PMID: 8910206]
Brown RE, Reymann KG. Class I metabotropic glutamate receptor agonists do not facilitate the induction of long-term potentiation in the dentate gyrus of the rat in vitro.
Neurosci Lett. 1995 Dec 29;202(1-2):73-6. [PMID: 8787834]
Brown RE, Reymann KG. Metabotropic glutamate receptor agonists reduce paired-pulse depression in the dentate gyrus of the rat in vitro.
Neurosci Lett. 1995 Aug 18;196(1-2):17-20. [PMID: 7501246]
Brown RE, Fedorov NB, Haas HL, Reymann KG. Histaminergic modulation of synaptic plasticity in area CA1 of rat hippocampal slices.
Neuropharmacology. 1995 Feb;34(2):181-90. [PMID: 7617144]
Brown RE, Rabe H, Reymann KG. (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not block theta burst-induced long-term potentiation in area CA1 of rat hippocampal slices.
Neurosci Lett. 1994 Mar 28;170(1):17-21. [PMID: 8041499]
Mol Neurobiol. 2004 Jun;29(3):243-59. Review. [PMID: 15181237]
Selbach O, Doreulee N, Bohla C, Eriksson KS, Sergeeva OA, Poelchen W, Brown RE, Haas HL. Orexins/hypocretins cause sharp wave- and theta-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling. Neuroscience. 2004;127(2):519-28. [PMID: 15262340]
Sergeeva OA, Korotkova TM, Scherer A, Brown RE, Haas HL. Co-expression of non-selective cation channels of the transient receptor potential canonical family in central aminergic neurones.
J Neurochem. 2003 Jun;85(6):1547-52. [PMID: 12787073]
Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins.
J Neurosci. 2003 Jan 1;23(1):7-11. [PMID: 12514194]
Brown RE, Sergeeva OA, Eriksson KS, Haas HL. Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline).
J Neurosci. 2002 Oct 15;22(20):8850-9. [PMID: 12388591]
Korotkova TM, Eriksson KS, Haas HL, Brown RE. Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro.
Regul Pept. 2002 Mar 15;104(1-3):83-9. [PMID: 11830281]
Korotkova TM, Haas HL, Brown RE. Histamine excites GABAergic cells in the rat substantia nigra and ventral
tegmental area in vitro.
Neurosci Lett. 2002 Mar 8;320(3):133-6. [PMID: 11852180]
Eriksson KS, Sergeeva O, Brown RE, Haas HL. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus.
J Neurosci. 2001 Dec 1;21(23):9273-9. [PMID: 11717361]
Stevens DR, Eriksson KS, Brown RE, Haas HL. The mechanism of spontaneous firing in histamine neurons.
Behav Brain Res. 2001 Oct 15;124(2):105-12. Review. [PMID: 11640962]
Doreulee N, Brown RE, Yanovsky Y, Godecke A, Schrader J, Haas HL. Defective hippocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice.
Synapse. 2001 Sep 1;41(3):191-4. [PMID: 11391779]
Brown RE, Stevens DR, Haas HL. The physiology of brain histamine.
Prog Neurobiol. 2001 Apr;63(6):637-72. Review. [PMID: 11164999]
Brown RE, Sergeeva O, Eriksson KS, Haas HL. Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat.
Neuropharmacology. 2001 Mar;40(3):457-9. [PMID: 11166339]
Doreulee N, Yanovsky Y, Flagmeyer I, Stevens DR, Haas HL, Brown RE. Histamine H(3) receptors depress synaptic transmission in the corticostriatal pathway.
Neuropharmacology. 2001;40(1):106-13. [PMID: 11077076]
Brown RE, Haas HL. On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus.
J Physiol. 1999 Mar 15;515 ( Pt 3):777-86. [PMID: 10066904]
Wilson RI, Godecke A, Brown RE, Schrader J, Haas HL. Mice deficient in endothelial nitric oxide synthase exhibit a selective deficit in hippocampal long-term potentiation.
Neuroscience. 1999;90(4):1157-65. [PMID: 10338286]
Manahan-Vaughan D, Reymann KG, Brown RE. In vivo electrophysiological investigations into the role of histamine in the dentate gyrus of the rat.
Neuroscience. 1998 Jun;84(3):783-90. [PMID: 9579783]
Selbach O, Brown RE, Haas HL. Long-term increase of hippocampal excitability by histamine and cyclic AMP.
Neuropharmacology. 1997 Nov-Dec;36(11-12):1539-48. [PMID: 9517424]
Fedorov NB, Brown RE, Reymann KG. Fast increases of AMPA receptor sensitivity following tetanus-induced
potentiation in the CA1 region of the rat hippocampus.
Neuroreport. 1997 Jan 20;8(2):411-4. [PMID: 9080418]
Brown RE, Reymann KG. Histamine H3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro.
J Physiol. 1996 Oct 1;496 ( Pt 1):175-84. [PMID: 8910206]
Brown RE, Reymann KG. Class I metabotropic glutamate receptor agonists do not facilitate the induction of long-term potentiation in the dentate gyrus of the rat in vitro.
Neurosci Lett. 1995 Dec 29;202(1-2):73-6. [PMID: 8787834]
Brown RE, Reymann KG. Metabotropic glutamate receptor agonists reduce paired-pulse depression in the dentate gyrus of the rat in vitro.
Neurosci Lett. 1995 Aug 18;196(1-2):17-20. [PMID: 7501246]
Brown RE, Fedorov NB, Haas HL, Reymann KG. Histaminergic modulation of synaptic plasticity in area CA1 of rat hippocampal slices.
Neuropharmacology. 1995 Feb;34(2):181-90. [PMID: 7617144]
Brown RE, Rabe H, Reymann KG. (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not block theta burst-induced long-term potentiation in area CA1 of rat hippocampal slices.
Neurosci Lett. 1994 Mar 28;170(1):17-21. [PMID: 8041499]
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