Dr. Meenakshi Alreja

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Yale University
School of Medicine
Psychiatry and Neurobiology
Associate Professor
Professional Headshot of Meenakshi Alreja

Mailing Address

34 Park Street
CMHC, W-215
Yale University
New Haven, Connecticut
United States

Contact Information

Phone: (203) 974-7762
Fax: (203) 974-7897
meenakshi.alreja@yale.edu

Qualifications

Postdoctoral, Yale University.
Ph.D., All India Institute of Medical Sciences.

Expertise and Research Interests

In the last 10 years, research in my laboratory has focussed on studies related to the neurobiology of the septohippocampal pathway with the view of comprehending the cellular mechanisms that underlie learning and memory related effects in this highly complex circuit. The septohippocampal pathway originates from the cholinergic and GABAergic cell bodies in the medial septal/diagonal band of Broca and terminates in virtually every region of the hippocampus. A loss/atrophy of the septohippocampal cholinergic neurons occurs in Alzheimer’s as well as in various other neurological disorders (such as in Parkinsonism, Down’s syndrome and Lewy body dementia) and possibly in normal aging too. In experimental animals, lesions of the septohippocampal pathway or a selective destruction of the cholinergic cell bodies produces deficits in learning and memory tasks related to the septohippocampal pathway. The resultant deficits in cognitive functioning have for a long time been attributed to the resultant loss in hippocampal acetylcholine, and as such therapeutic efforts have focussed on restoring hippocampal acetylcholine function using cholinesterase inhibitors and selective muscarinic receptor agonists. However, such treatments have only been of limited use.

Using a combination of state-of-the-art electrophysiological recording techniques we record the activity of selectively-labeled neurons in rat brain slices and examine the neurobiology of the septohippocampal pathway. The goal of our research is to understand how this pathway operates at the cellular level, and how it is modulated by neurotransmitters. It is hoped that this knowledge will provide direction for design of pharmacotherapies that can be used in the treatment of cognitive disorders

Other Expertise

I wish to be contacted by interested students (medical, graduate or undergraduates) as a potential research mentor/thesis advisor.

Industrial Relevance

Treatment of cognitive disorders that are associated with a loss of basal forebrain cholinergic neurons, such as Alzheimer's disease, Lewy body Dementia, etc.

Keywords

COS Keywords:

Addictions, Alzheimer's Disease, Down Syndrome, Drugs Or Drug Abuse, Electrophysiology, Human Learning and Memory, Neurobiology, Neuroscience, Neurotransmitters, Nicotine, Parkinson's Disease, Pharmacotherapy, Psychiatry, Signal Transduction.

Additional Terms:

Acetylcholine, Electrophysiology, GABA, Glutamate, Hypocretin, Learning and Memory, Neurotransmitters, Nicotine, Signal Transduction, Theta Rhythm.

Memberships

Society for Neuroscience

Honors and Awards

2001-2004, NARSAD Independent Investigator Award, NARSAD
1998-2000, NARSAD Young Investigator Award, NARSAD
1995-1997, NARSAD Young Investigator Award, NARSAD

Funding Received

  • NARSAD Independent Investigator Award: Septohippocampal cholinergic and GABAergic functions: modulation by neurotrophic factors, stress and antidepressant treatments., Sep 1, 2001 to Aug 31, 2004.
  • National Institutes of Health (NIH): Regulation of the septohippocampal pathway by stress, neurotrophins and antidepressant treatments, Jul 1, 2002 to Jun 30, 2007.
  • National Institutes of Health (NIH): Cholinergic and GABAergic mechanisms in the septohippocampal pathway., 2001 to 2011.

Publications

  • Wu M, Dumalska I, Morozova E, van den Pol AN, Alreja M (Feb 2009) Gonadotropin inhibitory hormone (GnIH) innervates, inhibits basal forebrain vGluT2-GnRH neurons via a direct postsynaptic mechanism., The Journal of physiology Abstract
  • Dumalska I, Wu M, Morozova E, Liu R, van den Pol A, Alreja M (Aug 2008) Excitatory effects of the puberty-initiating peptide kisspeptin and group I metabotropic glutamate receptor agonists differentiate two distinct subpopulations of gonadotropin-releasing hormone neurons., The Journal of neuroscience : the official journal of the Society for Neuroscience, 28 (32), 8003-13 Abstract
  • Morozova E, Wu M, Dumalska I, Alreja M (Jan 2008) Neurokinins robustly activate the majority of septohippocampal cholinergic neurons., The European journal of neuroscience, 27 (1), 114-22 Abstract
  • Xu C, Wu M, Morozova E, Alreja M (Oct 2006) Muscarine activates the sodium-calcium exchanger via M receptors in basal forebrain neurons., The European journal of neuroscience, 24 (8), 2309-13 Abstract
  • Xu C, Michelsen KA, Wu M, Morozova E, Panula P, Alreja M, Histamine Innervation and Activation of Septohippocampal GABAergic Neurones: Involvement of Local ACh Release., The Journal of Physiology, 561(Pt 3), 657-70, Dec 2004 Abstract
  • Wu M, Hajszan T, Xu C, Leranth C, Alreja M, Group I Metabotropic Glutamate Receptor Activation Produces a Direct Excitation of Identified Septohippocampal Cholinergic Neurons., Journal of Neurophysiology, 92(2), 1216-25, Aug 2004 Abstract
  • Wu M, Hajszan T, Xu C, Leranth C, Alreja M, Group I Metabotropic Glutamate Receptor Activation Produces a Direct Excitation of Identified Septohippocampal Cholinergic Neurons., Journal of Neurophysiology, 92(2), 1216-25, Aug 2004 Abstract
  • Wu M, Zaborszky L, Hajszan T, van den Pol AN, Alreja M, Hypocretin/orexin Innervation and Excitation of Identified Septohippocampal Cholinergic Neurons., The Journal of Neuroscience : the Official Journal of the Society for Neuroscience., 24(14), 3527-36, Apr 2004 Abstract
  • Hajszan T, Alreja M, Leranth C, Intrinsic Vesicular Glutamate Transporter 2-immunoreactive Input To Septohippocampal Parvalbumin-containing Neurons: Novel Glutamatergic Local Circuit Cells., Hippocampus, 14(4), 499-509, 2004 Abstract
  • Wu M, Newton SS, Atkins JB, Xu C, Duman RS, Alreja M, Acetylcholinesterase Inhibitors Activate Septohippocampal GABAergic Neurons Via Muscarinic But Not Nicotinic Receptors., The Journal of Pharmacology and Experimental Therapeutics, 307(2), 535-43, Nov 2003 Abstract
  • Wu M, Hajszan T, Leranth C, Alreja M, Nicotine recruits a local glutamatergic circuit to excite septohippocampal GABAergic neurons, The European Journal of Neuroscience, 18(5), 1155-68, September 2003 Abstract
  • Wu M, Zhang Z, Leranth C, Xu C, van den Pol AN, Alreja M, Hypocretin increases impulse flow in the septohippocampal GABAergic pathway: implications for arousal via a mechanism of hippocampal disinhibition, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience., 22(17), 7754-65, September 2002 Abstract
  • Alreja M, Wu M, Liu W, Atkins JB, Leranth C, Shanabrough M, Muscarinic tone sustains impulse flow in the septohippocampal GABA but not cholinergic pathway: implications for learning and memory, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience., 20(21), 8103-10, November 2000 Abstract
  • Wu M, Shanabrough M, Leranth C, Alreja M, Cholinergic excitation of septohippocampal GABA but not cholinergic neurons: implications for learning and memory, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience., 20(10), 3900-8, May 2000 Abstract
  • Alreja M, Shanabrough M, Liu W, Leranth C, Opioids suppress IPSCs in neurons of the rat medial septum/diagonal band of Broca: involvement of mu-opioid receptors and septohippocampal GABAergic neurons, The Journal of Neuroscience : the Official Journal of the Society for Neuroscience., 20(3), 1179-89, February 2000 Abstract
  • Nestler EJ, Alreja M, Aghajanian GK, Molecular control of locus coeruleus neurotransmission, Biological Psychiatry, 46(9), 1131-9, November 1999 Abstract
  • Liu W, Alreja M, Norepinephrine inhibits neurons of the intermediate subnucleus of the lateral septum via alpha2-adrenoceptors, Brain Research, 806(1), 36-54, September 1998 Abstract
  • Liu W, Kumar A, Alreja M, Excitatory effects of muscarine on septohippocampal neurons: involvement of M3 receptors, Brain Research, 805(1-2), 220-33, September 1998 Abstract
  • Liu W, Alreja M, Atypical antipsychotics block the excitatory effects of serotonin in septohippocampal neurons in the rat, Neuroscience, 79(2), 369-82, July 1997 Abstract
  • Alreja M, Liu W, Noradrenaline induces IPSCs in rat medial septal/diagonal band neurons: involvement of septohippocampal GABAergic neurons, Journal of Physiology, 494(Pt 1), 201-15, 1 Jul 1996 Abstract
  • Alreja M, Excitatory actions of serotonin on GABAergic neurons of the medial septum and diagonal band of Broca, Synapse, 22(1), 15-27, January 1996 Abstract
  • Alreja M, Aghajanian G K, Use of the whole-cell patch-clamp method in studies on the role of cAMP in regulating the spontaneous firing of locus coeruleus neurons, Journal of Neuroscience Methods, 59(1), 67-75, June 1995 Abstract
  • Alreja M, Aghajanian G K, QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons, Brain Research, 639(2), 320-4, 14 Mar 1994 Abstract
  • Nestler E J, Alreja M, Aghajanian G K, Molecular and cellular mechanisms of opiate action: studies in the rat locus coeruleus, Brain Research Bulletin, 35(5-6), 521-8, 1994 Abstract
  • Alreja M, Aghajanian G K, Opiates suppress a resting sodium-dependent inward current and activate an outward potassium current in locus coeruleus neurons, Journal of Neuroscience, 13(8), 3525-32, August 1993 Abstract
  • Garratt J C, Alreja M, Aghajanian G K, LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: intracellular studies in rat facial motoneurons, Synapse, 13(2), 123-34, February 1993 Abstract
  • Aghajanian G K, Alreja M, Nestler E J, Kogan J H, Dual mechanisms of opiate dependence in the locus coeruleus, Clinical Neuropharmacology, 15(Suppl 1 Pt A), 143A-144A, 1992 Abstract
  • Alreja M, Aghajanian G K, Activation of locus coeruleus (LC) neurones by cholera toxin: mediation by cAMP-dependent protein kinase, Neuroscience Letters, 134(1), 113-7, 16 Dec 1991 Abstract
  • Alreja M, Aghajanian G K, Pacemaker activity of locus coeruleus neurons: whole-cell recordings in brain slices show dependence on cAMP and protein kinase A, Brain Research, 556(2), 339-43, 16 Aug 1991 Abstract

Profile Details

Last Updated: 3/20/2009

COS Expertise ID #870762
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