Faculty Profile

Elda Arrigoni, PhD


Assistant Professor of Neurology, Harvard Medical School
Assistant in Neurology, Department of Neurology, Beth Israel Deaconess Medical Center

See publications


Research Interests

I am interested in the basic mechanisms that regulate sleep. All my work has been conducted using electrophysiological recordings in in vitro brain slice preparations. I am interested in understanding how at the cellular level the excitability of wake-promoting and sleep-promoting neurons is controlled and how neurotransmitters and neuromodulators such as orexin, dynorphin and adenosine affect neuronal circuitry through pre and postsynaptic actions. For several years I have been studying the mechanism of action of the sleep factor adenosine. In particular I investigated the electrophysiological effects of adenosine on neurons of the basal forebrain, brainstem and of the ventrolateral preoptic (VLPO) nucleus.

I am currently engaged in two major projects. In collaboration with Dr. Thomas Scammell, I am studying how orexin peptides promote wakefulness by exciting basal forebrain neurons that activate the cortex. In addition it has been known for quite some time, that orexin neurons also produce and probably release the inhibitory peptide dynorphin but yet little is known about which basal forebrain neurons respond to orexin and which to dynorphin. In this project I am interested in determining using whole-cell recording in brain slices the mechanisms through which orexin and dynorphin act on different basal forebrain neurons. In particular, I am interested in understanding the dynamics of the effects of orexin - an excitatory peptide - and dynorphin an inhibitory peptide – and the synergistic roles they play in activating the basal forebrain neurons to promote wakefulness.

In the second project, I am studying neurons of the sublaterodorsal (SLD) nucleus of the pons. These neurons have been recently implicated as crucial for eliciting muscular atonia during REM sleep. My colleagues, Drs. Lu and Saper, have recently found that glutamatergic REM-active neurons in the SLD directly project to the glycinergic/GABAergic premotorneurons in the spinal cord and have proposed a model in which these spinal projecting SLD neurons play a critical role in the generation of muscle atonia during REM sleep. My interest is to understand the physiology of REM sleep atonia. Because the SLD region contains a great variety of cell types, including several that may have no relation to REM atonia it is essential to be able to identify those neurons of the SLD that project to the spinal cord as these are almost certainly involved in generating atonia. For this purpose I have developed a method to label these cells using spinal cord injections of fluorescent tracers, thus enabling electrophysiological studies of these key neurons in a brain slice preparation. In this project I am studying the electrophysiological actions of the cholinergic, monoaminergic and orexinergic afferents to the SLD spinal projecting neurons using patch-clamp recordings in a slice preparation. It’s my belief that by identifying the circuitry that controls the REM atonia neurons we will provide a better understanding of the neurobiology of conditions such as REM sleep behavior disorder and cataplexy – two conditions in which the inappropriate activation of this REM atonia circuitry may occur.

Teaching

Instructor, Psychiatry Department, Brockton VA Medical Center, Harvard Medical School, 2001

Selected Publications

Arrigoni E, Mochizuki T, Scammell TE. Activation of the basal forebrain by the orexin/hypocretin neurones.
Acta Physiol (Oxf). 2009 Sep 1. [Epub ahead of print] [PMID: 19723027]

Arrigoni E, Lu J, Vetrivelan R, Saper CB. Long-term synaptic plasticity is impaired in rats with lesions of the ventrolateral preoptic nucleus.
Eur J Neurosci. 2009 Dec 3;30(11):2112-20. Epub 2009 Nov 25. [PMID: 20128848]

Arrigoni E, Rosenberg PA. Nitric oxide-induced adenosine inhibition of the hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent.
Eur. J. Neurosci. 2006;24:2471-2480. [PMID: 17100836]

Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, McCarley RW, Brown RE, Strecker RE. Hippocampal synaptic plasticity and special learning are impaired in rat model of sleep fragmentation.
Eur. J. Neurosci. 2006;23:2739-2748. [PMID: 16817877]

Arrigoni E, Chamberlin NL, Saper CB, McCarley RW. (2006). Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro.
Neuroscience 2006;140:403-413. [PMID: 16542780]

Arrigoni E, Crocker AJ, Saper CB, Greene RW, Scammell TE. Deletion of presynaptic adenosine A1 receptors impairs the recovery of synaptic transmission after hypoxia.
Neuroscience 2005;132:575-580. [PMID: 15837119]

Arrigoni E, Greene RW. Schaffer collateral and perforant path inputs activate different subtypes of NMDA receptors on the same CA1 pyramidal cell.
Br J Pharmacol. 2004;142:317-322. [PMID: 15155538]

Scammell TE, Arrigoni E, Thompson MA, Saper CB, Greene RW. Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector.
J Neurosci. 2003;23(13): 5762-5770. [PMID: 12843280]

Chamberlin NL, Arrigoni E, Chou T, Scammell TE, Greene RW, Saper CB. Effects of adenosine on GABAergic synaptic inputs to identified ventrolateral preoptic neurons.
Neuroscience 2003;119:913-918. [PMID: 12831851]

Basheer R, Arrigoni E, Thatte H, Greene RW, Ambudkar IS, McCarley RW. Adenosine induces IP3 receptor-mediated mobilization of intracellular calcium stores in basal forebrain cholinergic neurons.
J Neurosci. 2002;22(1):7680-7686. [PMID: 12196591]

Formenti A, De Simoni A, Arrigoni E, Martina M. Changes in extracellular Ca 2+ can affect the pattern of discharge in rat thalamic neurons.
J Physiol. 2001;535(1):33-45. [PMID: 11507156]

Arrigoni E, Rainnie DG, McCarley RW, Greene RW. Adenosine mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum.
J Neurosci. 2001;21(3):1076-1085. [PMID: 11157094]

Formenti A, Arrigoni E, Martina M, Taverna S, Avanzini G, Mancia M. Calcium influx in rat thalamic relay neurons through voltage-dependent calcium channels is inhibited by enkephalin.
Neuronsci Lett. 1995;201:21-24. [PMID: 8830303]

Formenti A, Arrigoni E, Mancia M. Low-voltage activated calcium channels are differently affected by nimodipine.
Neurorep. 1993;5:145-147. [PMID: 8111001]

Formenti A, Arrigoni E, Mancia M. Two distinct modulatory effects on calcium channels in adult rat sensory neurons.
Biophys J. 1993;64:1029-1037. [PMID: 8388263]

Formenti A, Arrigoni E, Sansone V, Arrigoni-Martelli E, Mancia M. Effects of acetyl-L-carnitine on the survival of adult rat sensory neurons in primary cultures.
Int J Devl Neuronsci. 1992;10:207-214. [PMID: 1442169]

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