Annalisa Scimemi | |
---|---|
Occupation | Neuroscientist |
Title | Associate Professor |
Academic background | |
Education | B.S., Università di Pisa, Italy Ph.D.,Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy |
Alma mater | https://www.sissa.it/ |
Academic advisors | John G. Nicholls, Enrico Cherubini, Dimitri M. Kullmann, Jeffrey S. Diamond |
Academic work | |
Discipline | Neuroscience |
Institutions | State University of New York at Albany University College London |
Website | https://sites.google.com/site/scimemilab2013/home https://www.albany.edu/biology/faculty/annalisa-scimemi |
Annalisa Scimemi (born 1974) is a neuroscientist on the faculty of the State University of New York at Albany (SUNY).
Born in Tuscany in 1974,Annalisa Scimemi studied Biological Sciences at the Universitàdi Pisa (1993–1998) as a first-generation college student. [1] [2] Her undergraduate thesis focused on the biophysical properties of calcium activated potassium channels in human erythrocytes in Steinert disease. [2] Scimemi earned her Ph.D. in Biophysics from the International School of Advanced Studies (SISSA/ISAS) in Trieste,Italy in 2001,studying the development of rhythmic circuits underlying locomotor-like behaviors in the opossum Monodelphis domestica,under the supervision of John G. Nicholls and Enrico Cherubini. [2]
In 2002,Scimemi joined the lab of Dimitri M. Kullmann at University College London. [3] At UCL,Scimemi studied central synapses and neurotransmitter spillover,working with Dimitri M. Kullmann,Dmitri A. Rusakov,Matthew C. Walker,and others. [4] [5] [6] [7] [8]
In 2005,Scimemi moved to the United States to join the lab of Jeffrey S. Diamond at the National Institutes of Health (NIH) in Bethesda,Maryland. [1] She continued to study hippocampal synapses,analyzing more specifically at the role of neuronal and astrocytic glutamate transporters in regulating inter-synaptic cross-talk. [1] [3] After earning an appointment as Research Fellow at NIH in 2010,she studied how the spatial distribution of calcium channels in the presynaptic active zone affects glutamate release at hippocampal synapses. [9] She also started new collaborations that branched her research focus to Alzheimer's disease. [10] [11]
Scimemi joined the faculty of the Department of Biology at SUNY Albany in 2013 and became an Adjunct Professor in the Department of Physics in 2015. She became an Associate Professor in 2019. In her lab,she aims to identify how neurons and astrocytes regulate encoding of spatial information and reward-based behaviors in health and disease. [12] [13] [14] [15]
Since 2017,she has served as an instructor for the summer course,Ion Channels in Synaptic &Neural Circuit Physiology, at the Cold Spring Harbor Laboratory. [16] Her scientific interests,though rooted in synaptic physiology,branch to other fields of neuroscience including systems neuroscience,which she fueled during her sabbatical in the lab of Bernardo Sabatini at Harvard Medical School.[ citation needed ]
Scimemi studies the functional properties of central synapses and how they are tuned by non-neuronal cells called astrocytes in neuropsychiatric disorders,using techniques such as electrophysiology,optogenetics,two-photon laser scanning microscopy,and reaction-diffusion computer simulations. [2] [17] Her works provide insights into how synaptic transmission changes in the hippocampus with circadian cycles. [2]
Scimemi's software "NRN-EZ" providing easy access to biophysical modeling of neurons (allowing distribution of synaptic inputs onto digitally reconstructed neurons) [18] was described in one of Scientific Reports' 100 most-downloaded research studies in 2023. [19]
A dendritic spine is a small membrane protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have a bulbous head, and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons. It has also been suggested that changes in the activity of neurons have a positive effect on spine morphology.
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell-to-cell signalling. EPSPs and IPSPs compete with each other at numerous synapses of a neuron. This determines whether an action potential occurring at the presynaptic terminal produces an action potential at the postsynaptic membrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.
In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress.
In neuroscience, a silent synapse is an excitatory glutamatergic synapse whose postsynaptic membrane contains NMDA-type glutamate receptors but no AMPA-type glutamate receptors. These synapses are named "silent" because normal AMPA receptor-mediated signaling is not present, rendering the synapse inactive under typical conditions. Silent synapses are typically considered to be immature glutamatergic synapses. As the brain matures, the relative number of silent synapses decreases. However, recent research on hippocampal silent synapses shows that while they may indeed be a developmental landmark in the formation of a synapse, that synapses can be "silenced" by activity, even once they have acquired AMPA receptors. Thus, silence may be a state that synapses can visit many times during their lifetimes.
Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.
Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.
In the brain, the perforant path or perforant pathway provides a connectional route from the entorhinal cortex to all fields of the hippocampal formation, including the dentate gyrus, all CA fields, and the subiculum.
Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.
A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own ligand.
In the hippocampus, the mossy fiber pathway consists of unmyelinated axons projecting from granule cells in the dentate gyrus that terminate on modulatory hilar mossy cells and in Cornu Ammonis area 3 (CA3), a region involved in encoding short-term memory. These axons were first described as mossy fibers by Santiago Ramón y Cajal as they displayed varicosities along their lengths that gave them a mossy appearance.
Synaptic gating is the ability of neural circuits to gate inputs by either suppressing or facilitating specific synaptic activity. Selective inhibition of certain synapses has been studied thoroughly, and recent studies have supported the existence of permissively gated synaptic transmission. In general, synaptic gating involves a mechanism of central control over neuronal output. It includes a sort of gatekeeper neuron, which has the ability to influence transmission of information to selected targets independently of the parts of the synapse upon which it exerts its action.
Gliotransmitters are chemicals released from glial cells that facilitate neuronal communication between neurons and other glial cells. They are usually induced from Ca2+ signaling, although recent research has questioned the role of Ca2+ in gliotransmitters and may require a revision of the relevance of gliotransmitters in neuronal signalling in general.
Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.
Potassium-chloride transporter member 5 is a neuron-specific chloride potassium symporter responsible for establishing the chloride ion gradient in neurons through the maintenance of low intracellular chloride concentrations. It is a critical mediator of synaptic inhibition, cellular protection against excitotoxicity and may also act as a modulator of neuroplasticity. Potassium-chloride transporter member 5 is also known by the names: KCC2 for its ionic substrates, and SLC12A5 for its genetic origin from the SLC12A5 gene in humans.
In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA.
Activity-regulated cytoskeleton-associated protein is a plasticity protein that in humans is encoded by the ARC gene. The gene is believed to derive from a retrotransposon. The protein is found in the neurons of tetrapods and other animals where it can form virus-like capsids that transport RNA between neurons.
The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells are found within the granular layer of the cerebellum, the dentate gyrus of the hippocampus, the superficial layer of the dorsal cochlear nucleus, the olfactory bulb, and the cerebral cortex.
An autapse is a chemical or electrical synapse from a neuron onto itself. It can also be described as a synapse formed by the axon of a neuron on its own dendrites, in vivo or in vitro.
Tripartite synapse refers to the functional integration and physical proximity of:
Dimitri Michael Kullmann is a British neurologist who is a professor of neurology at the UCL Institute of Neurology, University College London (UCL), and leads the synaptopathies initiative funded by the Wellcome Trust. Kullmann is a member of the Queen Square Institute of Neurology Department of Clinical and Experimental Epilepsy and a consultant neurologist at the National Hospital for Neurology and Neurosurgery.
This work seeks to advance understanding of neuronal circuits involved in spatial map representation — how space is represented and interpreted in the brain — and will support future strategies to treat diseases associated with hippocampal neural circuit dysfunction such as epilepsy and autism spectrum disorder
The project focuses on astrocytes, a type of non-neuronal cell in the brain, and a technique called optogenetics — using light to control brain activity. Dr. Scimemi's lab is at the forefront of this technology, which relies on a multidisciplinary blend of electrophysiology, imaging, computational and behavioral approaches