Attila Losonczy

Last updated
Attila Losonczy
Born1974 (age 48–49)
Nagykanizsa, Hungary
Alma mater
Awards
Scientific career
Fields Circuit neuroscience
Institutions Columbia University Medical Center
Doctoral advisor Zoltan Nusser

Attila Losonczy (born 1974) is a Hungarian neuroscientist, Professor of Neuroscience at Columbia University Medical Center. [1] Losonczy's main area of research is on the relationship between neural networks and behavior, specifically with regard to learning in the hippocampus.

Contents

His group conducts research on spatial navigation and episodic learning in animal models as well as the pathology of cognitive memory deficits in neurodegenerative disorders and psychiatric disorders such as PTSD and anxiety. [2] [3] Losonczy is currently working on developing in vivo imaging methods using two-photon microscopy and calcium imaging to simultaneously image hundreds of hippocampal place cells in conscious mice performing spatial tasks. [4] [5]

Early life and education

Attila Losonczy was born in Nagykanizsa, Hungary, in 1974. He received the MD degree from the University of Pécs Medical School in 1999, and subsequently the PhD degree at Semmelweis University in Neurobiology in 2004 with a thesis entitled "Underlying mechanisms of short-term synaptic plasticity at identified central synapses," advised by Zoltan Nusser. In 2003, he moved from Hungary to the United States; from 2003 to 2006, Losonczy was a postdoctoral fellow at Louisiana State University with Jeffrey Magee. In 2006, he served as a postdoctoral fellow with Gero Miesenböck at Yale University. [1]

Career

From 2007 to 2009, Losonczy worked as a research specialist at Howard Hughes Medical Institute, again working with Magee. [1]

In 2009, Losonczy joined the faculty at Columbia University as a professor. [1] Since 2010, Losonczy has been a member of the Kavli Institute for Brain Science. In 2011, Losonczy was named a Searle Scholar. In 2013, he was awarded the NARSAD Young Investigator Award. Losonczy was awarded the BRAIN Initiative Award by the National Institute of Health in two consecutive years, 2014 and 2015. [4] Losonczy is a journal reviewer for Science , Cell , Nature Neuroscience , and Neuron , among others. [1]

Losonczy and his PhD student Matthew Lovett-Barron uncovered the role of interneurons in fear memory formation in the hippocampus using in vivo imaging and optogenetics. [5] By deactivating these interneurons, Losonczy showed that fear memories could be suppressed and contextual fear conditioning could thus be prevented. This discovery is significant to research into the mechanism psychiatric disorders such as post-traumatic stress disorder. [2]

In 2015, Losonczy and his PhD student Nathan Danielson discovered the role of neurogenesis in the dentate gyrus in memory formation and pattern separation. [6] [7] To perform this study, Losonczy used two-photon microscopy and calcium imaging to image newborn granule cells in the mouse hippocampus and compare them with mature neurons as the mice traveled through subtly different contexts. [8] No previous work had been able to study the roles of newborn and mature cells in the dentate gyrus as it was not previously possible to image the dentate gyrus at all, much less observe individual dentate gyrus cells in detail, as it lies too deep in the midbrain. [9] To overcome these obstacles, Losonczy and his collaborators pioneered and implemented several novel techniques to be used simultaneously including the implantation of a miniature microscope into the brains of mice, genetically modifying mouse neurons to fluoresce, and optogenetically silencing a subset of neurons. [10] This discovery repudiated the pre-existing theory that newborn neurons carried new memories. Rather, Losonczy found that the firing of older cells was more localised and newborn neurons fire indiscriminately, not taking on a stereotyped firing pattern until they got older. This suggests that the more excitable newborn neurons are better at encoding new stimuli than more mature neurons. [11] This discovery is significant, as anxiety, depression, and posttraumatic stress disorder are thought to be associated with failures in pattern separation. [8] [10]

Bibliography

Related Research Articles

<span class="mw-page-title-main">Entorhinal cortex</span> Area of the temporal lobe of the brain

The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time. The EC is the main interface between the hippocampus and neocortex. The EC-hippocampus system plays an important role in declarative (autobiographical/episodic/semantic) memories and in particular spatial memories including memory formation, memory consolidation, and memory optimization in sleep. The EC is also responsible for the pre-processing (familiarity) of the input signals in the reflex nictitating membrane response of classical trace conditioning; the association of impulses from the eye and the ear occurs in the entorhinal cortex.

<span class="mw-page-title-main">Hippocampus</span> Vertebrate brain region involved in memory consolidation

The hippocampus is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper, and the dentate gyrus.

<span class="mw-page-title-main">Limbic system</span> Set of brain structures involved in emotion and motivation

The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.

<span class="mw-page-title-main">Dentate gyrus</span> Region of the hippocampus in the brain

The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute to the formation of new episodic memories, the spontaneous exploration of novel environments and other functions.

<span class="mw-page-title-main">Adult neurogenesis</span> Generating of neurons from neural stem cells in adults

Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.

The entorhinal cortex (EC) is a major part of the hippocampal formation of the brain, and is reciprocally connected with the hippocampus.

<span class="mw-page-title-main">Temporal lobe epilepsy</span> Chronic focal seizure disorder

Temporal lobe epilepsy (TLE) is a chronic disorder of the nervous system which is characterized by recurrent, unprovoked focal seizures that originate in the temporal lobe of the brain and last about one or two minutes. TLE is the most common form of epilepsy with focal seizures. A focal seizure in the temporal lobe may spread to other areas in the brain when it may become a focal to bilateral seizure.

<span class="mw-page-title-main">Perforant path</span>

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.

Brian R. Christie is a Professor of Medicine and Neuroscience at The University of Victoria. He helped found the Neuroscience Graduate Program at the University of Victoria and served as its director from 2010–2017. He is a Michael Smith Senior Scholar Award winner. Christie received his PhD in 1992 from the University of Otago before doing postdoctoral work with Daniel Johnston at Baylor College of Medicine and Terrence Sejnowski at the Salk Institute for Biological Studies, and then became Assistant Professor at the University of British Columbia. Promoted to Associate Professor in 2007. Full Professor in 2013.

<span class="mw-page-title-main">Mossy fiber (hippocampus)</span> Pathway in the hippocampus

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. The axons that make up the pathway emerge from the basal portions of the granule cells and pass through the hilus of the dentate gyrus before entering the stratum lucidum of CA3. Granule cell synapses tend to be glutamatergic, though immunohistological data has indicated that some synapses contain neuropeptidergic elements including opiate peptides such as dynorphin and enkephalin. There is also evidence for co-localization of both GABAergic and glutamatergic neurotransmitters within mossy fiber terminals. GABAergic and glutamatergic co-localization in mossy fiber boutons has been observed primarily in the developing hippocampus, but in adulthood, evidence suggests that mossy fiber synapses may alternate which neurotransmitter is released through activity-dependent regulation.

The trisynaptic circuit, or trisynaptic loop is a relay of synaptic transmission in the hippocampus. The circuit was initially described by the neuroanatomist Santiago Ramon y Cajal, in the early twentieth century, using the Golgi staining method. After the discovery of the trisynaptic circuit, a series of research has been conducted to determine the mechanisms driving this circuit. Today, research is focused on how this loop interacts with other parts of the brain, and how it influences human physiology and behaviour. For example, it has been shown that disruptions within the trisynaptic circuit leads to behavioural changes in rodent and feline models.

<span class="mw-page-title-main">Hippocampus anatomy</span>

Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of the brain. It has a distinctive, curved shape that has been likened to the sea-horse monster of Greek mythology and the ram's horns of Amun in Egyptian mythology. This general layout holds across the full range of mammalian species, from hedgehog to human, although the details vary. For example, in the rat, the two hippocampi look similar to a pair of bananas, joined at the stems. In primate brains, including humans, the portion of the hippocampus near the base of the temporal lobe is much broader than the part at the top. Due to the three-dimensional curvature of this structure, two-dimensional sections such as shown are commonly seen. Neuroimaging pictures can show a number of different shapes, depending on the angle and location of the cut.

<span class="mw-page-title-main">Medial septal nucleus</span>

The medial septal nucleus (MS) is one of the septal nuclei. Neurons in this nucleus give rise to the bulk of efferents from the septal nuclei. A major projection from the medial septal nucleus terminates in the hippocampal formation.

<span class="mw-page-title-main">Granule cell</span> Type of neuron with a very small cell body

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.

<span class="mw-page-title-main">Glucocorticoids in hippocampal development</span> HippoCampus

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The hippocampus participates in the encoding, consolidation, and retrieval of memories. The hippocampus is located in the medial temporal lobe (subcortical), and is an infolding of the medial temporal cortex. The hippocampus plays an important role in the transfer of information from short-term memory to long-term memory during encoding and retrieval stages. These stages do not need to occur successively, but are, as studies seem to indicate, and they are broadly divided in the neuronal mechanisms that they require or even in the hippocampal areas that they seem to activate. According to Gazzaniga, "encoding is the processing of incoming information that creates memory traces to be stored." There are two steps to the encoding process: "acquisition" and "consolidation". During the acquisition process, stimuli are committed to short term memory. Then, consolidation is where the hippocampus along with other cortical structures stabilize an object within long term memory, which strengthens over time, and is a process for which a number of theories have arisen to explain the underlying mechanism. After encoding, the hippocampus is capable of going through the retrieval process. The retrieval process consists of accessing stored information; this allows learned behaviors to experience conscious depiction and execution. Encoding and retrieval are both affected by neurodegenerative and anxiety disorders and epilepsy.

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<span class="mw-page-title-main">Hippocampus proper</span> Part of the brain of mammals

The hippocampus proper refers to the actual structure of the hippocampus which is made up of three regions or subfields. The subfields CA1, CA2, and CA3 use the initials of cornu Ammonis, an earlier name of the hippocampus.

The supramammillary nucleus (SuM), or supramammillary area, is a thin layer of cells in the brain that lies above the mammillary bodies. It can be considered part of the hypothalamus and diencephalon. The nucleus can be divided into medial and lateral sections. The medial SuM, or SuMM, is made of smaller cells which release dopamine and give input to the lateral septal nucleus. The lateral SuM, or SuML, is made of larger cells that project to the hippocampus.

Christine Denny is an American neuroscientist and Associate Professor of Clinical Neurobiology in Psychiatry in the Department of Psychiatry at Columbia University Irving Medical Center in New York City. Denny investigates the molecular mechanisms underlying learning and memory. She developed a novel technique to label neurons that encode specific memories. She used this technique to probe what happens to hippocampal memory traces in different disease states.

References

  1. 1 2 3 4 5 "Attila Losonczy Biography" (PDF). Columbia University. Retrieved 11 April 2016.
  2. 1 2 Hogenboom, Melissa (20 February 2014). "Fear suppressing neurons found". BBC News. Retrieved 11 April 2016.
  3. ↑ Losonczy, Attila. "Central Directions of the Lab". Losonczy Lab. Columbia University. Retrieved 11 April 2016.
  4. 1 2 Borthwick, Lindsey. "Modeling the Brain on 'Replay': A Q&A with Attila Losonczy". The Kavli Foundation. Retrieved 11 April 2016.
  5. 1 2 Lovett-Barron, Matthew; Losonczy, Attila (21 February 2014). "Dendritic Inhibition in the Hippocampus Supports Fear Learning". Science. 343 (6173): 857–863. Bibcode:2014Sci...343..857L. doi:10.1126/science.1247485. PMC   4018419 . PMID   24558155.
  6. ↑ Futurism (15 March 2016). "Scientists Get Their First Glimpse At How New Memories Are Born". Futurism. Retrieved 11 April 2016.
  7. ↑ Hernandez, Daniela. "The Mysteries of How Newborn Cells May Help Form Memories". Wall Street Journal. Retrieved 11 April 2016.
  8. 1 2 Underwood, Emily (10 March 2016). "Newborn neurons keep memories crisp and fresh". Science News. Retrieved 11 April 2016.
  9. ↑ Offord, Catherine (14 March 2016). "Observing Nascent Neurons in Action". The Scientist. Retrieved 11 April 2016.
  10. 1 2 Hamzelou, Jessica. "Newborn neurons observed in a live brain for first time". New Scientist. Retrieved 11 April 2016.
  11. ↑ Danielson, Nathan; Kaifosh, Patrick; Lovett-Barron, Matthew; Tsai, Joseph; Denny, Christine; Balough, Elizabeth; Goldberg, Alexander; Drew, Liam; Hen, Rene; Losonczy, Attila; Kheirbek, Mazen (6 April 2016). "Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding". Neuron. 90 (1): 101–112. doi:10.1016/j.neuron.2016.02.019. PMC   4962695 . PMID   26971949.
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