Past events | The department of Brain Sciences

All events, All years

Neuroprotection in Multiple Sclerosis Translation of Experimental Therapy Results into Clinical Studies

Lecture

Date:

Wednesday, April 28, 2010

Hour: 14:30

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Prof. Mathias Baehr

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Head, Dept of Neurology University of Gottingen Medical School, Germany

Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) in brown Norway rats mimicks neurodegenerative aspects of multiple sclerosis (MS). In this model, optic neuritis leads to acute axonal lesions and consecutive apoptotic cell death of RGCs, whose axons form the optic nerve. The intracellular mechanisms of RGC apoptosis resemble those described after surgical transection of the optic nerve. These mechanisms involve shifts in the expression of Bcl-2 family members, mitogen-activated protein kinases , and the phosphatidylinositol-3-kinase/Akt pathway. Current research on neurodegenerative aspects in EAE or MS is focused on developing treatment strategies that inhibit degeneration of axons as well as protection of the neuronal cell body from apoptotic cell death. The concept of achieving neuroprotective effects by successful treatment of inflammation and autoimmunity was supported by studies showing a close association of axonal damage and inflammation. However, trials evaluating anti-inflammatory therapies in MS patients have shown that elimination of the inflammatory component of the disease does not necessarily stop progression of brain and spinal cord atrophy. Methylprednisolone, the standard treatment of autoimmune optic neuritis, accelerates visual recovery, but it does not influence the final visual outcome. In MOG-induced optic neuritis, even detrimental effects of anti-inflammatory treatment with methylprednisolone on the survival of RGCs were observed. On the other hand, blocking apoptosis signals in neurons without simultaneously treating inflammation-induced axon degeneration does not lead to functionally relevant results: Although application of Epo as well as CNTF increases survival rates of RGCs during MOG-induced optic neuritis, visual acuity in these animals remains poor due to severe and ongoing degeneration of optic nerve axon fibers. These observations led to a hypothesis that can easily be transferred to the situation in MS: Due to the much larger proportion of white matter in the human brain, preventing apoptosis of neuronal cell bodies alone might not find its expression in clinical scores and neurological function. Therefore, neuroprotective approaches in combination with the established disease-modifying therapies might be more promising. Simultaneous application of methylprednisolone and Epo or Minocycline in MOG-induced optic neuritis resulted in a functional, electrophysiological improvement of optic nerves and RGCs as well as in increased neuronal and axonal survival The lecture will outline the transfer of these experimental approaches into a clinical trial and discuss other new neuroprotective and regenerative strategies.

Habituation and adaptation in the barn owl

Lecture

Date:

Tuesday, April 27, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Yoram Gutfreund

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Dept of Physiology and Biophysics Faculty of Medicine, Technion, Haifa

Habituation is the most basic form of learning yet very little is known about the underlying mechanisms. In our lab, we use the pupil dilation reflex of the barn owl as a model system to study habituation. In barn owls the pupils dilate in response to an unexpected stimulus. This response habituates dramatically if the stimulus is repeated. The advantage of using the PDR is that it can be measured non-invasively in immobilized and even anaesthetized barn owls. This allows for an easy combination of physiological experiments with behavioral experiments. In my talk I will describe recent experiments addressing the effects of microstimulation in the optic tectum on the PDR and will show that neural responses in the optic tectum are correlated with the habituation of the PDR. These findings link the optic tectum with habituation processes.

Stress related disorders induces neuroadaptations in the Nucleus-Accumbens spontaneous activity and in Hippocampaly evoked Accumbens activity

Lecture

Date:

Thursday, April 22, 2010

Hour: 13:00

Location:

Nella and Leon Benoziyo Building for Brain Research

Yaron Penn

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Zangen Group, Dept of Neurobiology, WIS

Stress related dissorders are likely to result from atypical processing and integration of information by several serieses of neural networks. These dissorders have been associated with neuroadaptations found at molecular and cellular levels within reward-related brain regions. The nucleus accumbens (NAcc) is a central component of the reward system. Convergence of glutamatergic innervations from limbic and cortical structures under intense dopaminergic modulations, places the NAcc as the major site for integration of emotional salience, contextual constraints and executive/motor plans. In the current study we found the medial shell of the NAcc to exhibit life-experience dependant adaptations. In animals exposed to chronic mild stress (CMS), there was an increase in spontaneous patterned network activity, synaptic potentiation of vSub innervations and increased GluR1 levels in the NAcc shell. In contrast, the ability to sustain time-locked, hippocampally evoked, network response was strongly reduced. That and more, we found evidence for short- and long- term plasticity in the vSub-NAcc pathway of CMS animals, but not in their control counterparts. Over all, we argue that stressful life-experience is associated with in-vivo, long-term functional adaptations in the reward system. The individual animal’s life experience history was found to leave its mark on the NAcc network activity, properties and response. Taken together with the life-experience dependent plasticity results, these adaptations are suggested to reflect part of the adverse functional mechanism which guide behavioral deficits in stress related dissorders.

What one can learn about the barrel cortex without touching a whisker

Lecture

Date:

Wednesday, April 21, 2010

Hour: 12:30

Location:

Nella and Leon Benoziyo Building for Brain Research

Michael Okun

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Lampl Group, Dept of Neurobiology, WIS

The presentation will cover the projects in the lab of Dr. Ilan Lampl in which I took part during the last several years. Specifically, I intend to speak about the following topics: (i) existence of repeating motifs in subthreshold neuronal activity in the cortex, and its relationship to the synfire chain model; (ii) balance of excitation and inhibition in the cortex; and (iii) understanding spike-LFP relationships using intracellular recordings. I will also briefly describe some of our ongoing and future research projects.

Olfactory Information Processing in Awake Mouse: Smell the Time

Lecture

Date:

Wednesday, April 14, 2010

Hour: 15:00

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Dr. Dmitry Rinberg

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Janelia Farm Research Campus Howard Hughes Medical Institute

The envious brain: to the neural basis of social inequity

Lecture

Date:

Tuesday, April 13, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Simone Shamay-Tsoory

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Dept. of Psychology University of Haifa

A large corpus of evidence concerning social comparison processes indicates that relative material payoffs affect people’s well-being and behavior. Envy and schadenfreude are emotions related to social comparison. Envy is a negative reaction in the face of another person’s good fortune while schadenfreude, is the joy about the misfortune of another. We suggested that the neural network which mediates envy and schadenfreude involves the 'mentalizing network' and the reward/punishment systems. To examine our model we conducted a lesion study, an fMRI study and a study involving administration of oxytocin. The results confirm our model and shwo differential patterns of activation in the reward and mentalizing networks in envy and schadenfreude. These studies support the role of the metalizing system (particularly the medial prefrontal cortex) in these emotions. The pattern of activation in the ventral striatum suggests that winning money can seem like a loss when another person wins a larger amount. Likewise, losing money can seem like a gain when another person loses more. Finally, we demonstrate that the oxytocinergic system modulates the feeling of envy and schadenfruede. Specifically, intranasal administration of oxytocin increases ratings of envy and schadenfreude in competitive situations, suggesting that this hormone has a general role in negative as well as positive social behaviors. Although it has been well established that humans are motivated to seek rewards and avoid punishments, our studies demonstrate that humans are as sensitive to social comparisons, that even a loss can induce joy when it is compared to another's greater loss. These processes seem to be mediated by the reward system and the oxytocinegic system

Understanding neuronal circuits in the mammalian olfactory bulb

Lecture

Date:

Wednesday, April 7, 2010

Hour: 15:00

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Dr. Dinu Florin Albeanu

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Cold Spring Harbor Laboratory

Abstract: In many regions of the brain, neurons form an ordered representation of the outside world. For example, the 'homunculus' of the somatosensory cortex is a point-to-point topographic map of the body surface onto the brain surface. The spatially organized convergence of sensory inputs often leads to similar response properties in target neurons that are in close vicinity. Whether their individual information content is redundant or independent depends on the circuit architecture (the interplay between common input, lateral signals and feedback from other brain areas) and the computational goals of the network. In the mammalian olfactory bulb (OB), sensory neurons expressing the same type of olfactory receptor (~10,000) converge in tight focus, forming clusters of synapses called glomeruli (~2,000). From each glomerulus, a few dozen mitral cells (principal output neurons of the OB) carry the output further to the cortex. The mitral cells, typically have only one primary dendrite that projects to a single glomerulus, but can sample inputs on their primary and secondary dendrites from functionally diverse glomeruli via several types of interneurons. Thus, a few dozen mitral cells share input from the same parent glomerulus, but may have different inhibitory surrounds. In the first part of this talk, I will discuss the topographic layout of glomeruli on the bulb - the olfactory map. How precise is this map within and across two species: mouse and rat? How does its structure relate to odor processing? Do glomeruli that are responsive to structurally similar odor molecules have a tendency to lie next to each other? In other words, is there a chemotopic map? In the second part of the talk, I will focus on probing the odor response properties of mitral cells using extracellular recordings and an optogenetic strategy to ask whether the OB is more than a relay station. Do mitral cells receiving common input from the same parent glomerulus carry redundant information about odors to cortex? I will conclude by describing novel strategies that allow monitoring the input-output transfer function of the OB via multi-photon microscopy imaging of bulb neurons activity in the same animal, in different states of the circuit. Link for further information: http://www.cshl.edu/public/SCIENCE/albeanu.html

Recording from human neurons in vivo: electro-olfactograms

Lecture

Date:

Thursday, March 25, 2010

Hour: 10:30

Location:

Nella and Leon Benoziyo Building for Brain Research

Hadas Lapid

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Sobel Group, Dept of Neurobiology, WIS

The olfactory epithelium offers a rare opportunity to record sensory activity directly from olfactory receptor neurons in awake behaving humans. A potential method to probe this neural sheet is by recording a local field potential (LFP) known as the Electro-Olfactogram (EOlfG). Although this method is considered a standard tool in anesthetized animals, it has gained only little attention in humans mostly due to the technical barriers in targeting this tissue. We first validated EOlfGs as a tool for quantification of the evoked olfactory response. Specifically, we found that EOlfGs were concentration dependent and odorant specific. We then turned to ask how specific odorant qualities are reflected in the EOlfG. Initial findings suggested that EOlfG area under the curve was correlated with an aspect of physicochemical odorant structure that we refer to as "molecular compactness". In summary, we find EOlfGs a promising tool for elucidating the link between an olfactory stimulus, its evoked neuronal response, and its percept.

Molecular Neurobiology of Social Bonding: Implications for Autism Spectrum Disorders

Lecture

Date:

Tuesday, March 23, 2010

Hour: 13:30

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Prof. Larry Young

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Dept of Psychiatry and Behavioral Sciences Emory University School of Medicine, Atlanta GA

Social relationships are at the core of every healthy society and the quality of early social attachments contributes to emotional and social development. I will discuss the neurobiological mechanisms underlying social attachment and bonding, as well as the impact of early life social experience on later life social relationships. The highly social and monogamous prairie vole is an ideal animal model for investigating the biological mechanisms of social attachment and bonding. Studies in voles have revealed that the neuropeptides oxytocin and vasopressin promote social bonding. Furthermore, variation in the oxytocin and vasopressin systems contributes to diversity in social behavior both across species and within populations. I will discuss the genetic mechanisms giving rise to diversity in social organization in voles. Finally I will discuss parallels between these studies in voles and recent studies in humans which suggest that these mechanisms are highly conserved from rodent to man. These observations have important implications for psychiatric disorders characterized by disruptions in social behavior, including autism.

Binding elements to a whole, problem and solution

Lecture

Date:

Tuesday, March 16, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Prof. Moshe Abeles

|

Bar-Ilan University

Firing rates of neurons cannot explain how we compose complex mental representations from more primitive elements. If spike time matters compositionality can easily be explained. This can easily be achieved by synfire chains. We provide indirect evidence that monkey scribbling is generated by synfire chains. Furthermore, we show by simulations that synfire chains in two distinct areas with a few random connections may learn to resonate with each other. We also show how many representations of mental elements may reside in the same small area, when practically all neurons participate in all the presentations, and yet what is represented can be identified in a few ms. In simulations, the global activity may oscillate in the gamma range without any oscillatory activity of individual neurons. When the activity of synfire chains in the two regions are bound the oscillations synchronize. We illustrate such processes in MEG recordings.

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All events, All years

Dogs, Rats and Explosives Detection

Lecture

Date:

Tuesday, February 9, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Allen Goldblatt

|

Center for Applied Animal Behavior for Security Purposes

Dogs are the gold standard in explosives detection. They are fast, mobile, sensitive and not prone to making false positive responses. More and more security and defense agencies are using dogs as explosives detectors in the field, at ports of entry, and in any area where there is a threat of terrorism. Surprisingly and unfortunately there has been very little published and/or peer reviewed research on the variables that can affect the explosives detection dog (EDD). Therefore in order to provide a scientific basis for the training and maintenance of explosives detection dogs, it is necessary to extrapolate from the extensive olfactory research which has been published on rodents and humans. The question then arises as to how applicable the research on rats and humans is to the training and maintenance of the EDD. Recent research on dogs suggests that the research on rodents and humans may be of limited applicability to EDDs. This research will be discussed and possible explanations for the discrepancies offered.

NEURAL CODES AND COMPUTATIONS UNDERLYING ODOR-GUIDED DECISIONS IN THE RAT

Lecture

Date:

Thursday, February 4, 2010

Hour: 13:30

Location:

Gerhard M.J. Schmidt Lecture Hall

Prof. Zach Mainen

|

Champalimaud Neuroscience Programme at the Instituto Gulbenkian de Ciência, Portugal

Abstract: For several years we have been studying the performance of rats in an odor mixture categorization task, in which an animal makes a left/right spatial choice instructed by the dominant component of a binary odor mixture. In order to better understand the neural basis of such odor guided decisions we have recorded ensembles of tens of neurons in several different brain regions during the performance of this task. I will present findings from these studies, emphasizing the nature of neural representations in the primary olfactory cortex as well as two downstream structures, orbitofrontal cortex and superior colliculus. My talk will emphasize the read-out and evaluation of sensory information by higher order brain regions and the contributions of non sensory variables to the performance of perceptual tasks.

Zebrafish shed light on the vertebrate circadian clock system

Lecture

Date:

Tuesday, February 2, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Yoav Gothilf

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Dept of Neurobiology Tel Aviv University

The core circadian clock in zebrafish is similar to that described in mammals. Nevertheless, there are some notable features that render the zebrafish an attractive model for chronobiologists 1) Circadian rhythms appear early in life; rhythms of melatonin production in the pineal gland begin two days after fertilization. 2) Zebrafish peripheral clock-containing structures and cell lines are directly light-entrainable. 3) The zebrafish model offers a plethora of molecular-genetics techniques, such as gene knockdown and over expression, transgenesis, genome-wide transcriptome analysis (gene chip) and bioinformatics tools, including the entire genomic sequence. Studies in our lab have indicated that circadian rhythms of pineal aanat2 expression appear on the third day of development and that light exposure is mandatory for the development of this rhythm. Additionally, light induces the expression of period2 (per2) in the pineal gland; an important event in the development of the pineal circadian clock. Utilization of the light-entrainable zebrafish cell lines enables to study the mechanisms underlying light-induced per2 expression and light-entrainment. These cell-based studies are being complimented by in vivo studies in wild type and per2:EGFP transgenic zebrafish line, where gene knockdown and over expression are used to determine the involvement of putative transcription factors in this process. Further, a genome-wide examination of gene expression allows the detection of known and novel rhythmic and light-induced genes, and their function in the pineal gland can be investigated in vivo by current molecular-genetic techniques. In conclusion, the use of zebrafish advances our understanding of the mechanisms underlying clock function, light-entrainment and functional development of the pineal gland.

Sleep, circadian rhythms and hypocretin neuronal networks in zebrafish

Lecture

Date:

Tuesday, January 26, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Lior Appelbaum

|

Dept of Psychiatry and Behavioral Science Stanford University

Sleep and circadian rhythms are functionally important in all vertebrates and sleep disorders affect millions of people worldwide. While we understand that the timing and quality of sleep are regulated by circadian and homeostatic processes, the function of sleep is still enigmatic. Increasing evidence points to a role for sleep in maintaining “synaptic homeostasis”. This hypothesis suggests increases in global synaptic strength during wakefulness followed by a decrease during sleep, primarily in memory-related circuits. Hypocretins/orexins (HCRT) are neuropeptides that are important sleep-wake regulators and HCRT deficiency causes narcolepsy in humans and mammalian models. We have functionally characterized the HCRT system in zebrafish, a diurnal transparent vertebrate that is ideally suited to study neuronal anatomy along with sleep and circadian rhythms in vivo. We use time-lapse two-photon imaging in living zebrafish of pre- and post-synaptic markers to determine the dynamics of synaptic modifications during day and night and after manipulation of candidate genes. Video-tracking systems are used to monitor activity and sleep in order to link changes in gene expression and synaptic plasticity with behavioral output. We have found a functional HCRT neurons-pineal gland circuit that is able to modulate melatonin production and sleep consolidation. Importantly, we observed clock-controlled rhythmic variation in synapse number in HCRT axons projecting to the pineal gland. Furthermore, we cloned NPTX2b (neuronal activity-regulated pentraxin, NARP), a protein implicated in AMPA receptor clustering, and showed that it is a clock-controlled gene that regulates rhythmic synaptic plasticity in HCRT axons as well as the sleep promoting effect of melatonin. These data provide real-time, in vivo evidence of circadian regulation of structural synaptic plasticity. Building on this experimental approach, we developed several transgenic lines expressing a variety of excitatory and inhibitory synaptic markers and neuronal activity tools using the GAL4-UAS system. This opens the possibility of studying synaptic plasticity in other circuits, such as those involved in memory formation and learning, which are known to be sleep-dependent in mammals. Such an approach offers the opportunity to study synaptic plasticity in response to pharmacological and behavioral challenges or after genetic manipulation of key synaptic proteins, with complementary monitoring of the resulting behavior in a living vertebrate.

A BRAIN FULL OF MAPS

Lecture

Date:

Tuesday, January 19, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Dori Derdikman

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Kavli Institute for Systems Neuroscience and The Centre for the Biology of Memory Norwegian University for Science and Technology Trondheim, Norway

Grid cells are neurons in the medial entorhinal cortex whose firing locations in a walking animal define a periodic triangular array covering the two-dimensional space in which the rat is moving. Grid cells can be used to calculate the position of the rat in the environment, suggesting that they contribute to representing the concept of space in the brain. It was not known whether the triangular array represented by each grid cell was covering the whole environment, or whether it is fragmented into semi-independent sub-maps. We thus compared two conditions. First the rat was put into an open-field arena, where we could record the periodic triangular grids. Next, we inserted walls into the open-field in order to create a set of corridors such that the rat had to pass from one corridor to the next in a zigzag path we termed this type of test the “hairpin” maze). If the triangular map was covering the whole world, the position of the grid nodes should not have been affected by the insertion of the walls. However, insertion of the walls broke up the grid pattern. The positions in the grid map where the breaking-up occurred were at the turning points between compartments - where one corridor ended and a new one started. We thus concluded that the grid was fragmented; it is “reset’ when the rat is moving from one compartment to another compartment. This implies that the representation of space in the brain is built of multiple independent sub-maps that each cover only a small section of the environment.

Changing Human Fear:Brain Mechanisms Underlying Emotional Control and Flexibility

Lecture

Date:

Tuesday, January 12, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Daniela Schiller

|

New York University

Learned fear is a process allowing quick detection of associations between cues in the environment and prediction of imminent threat ahead of time. Adaptive function in a changing environment, however, requires organisms to quickly update this learned information and have the ability to hinder fear responses when predictions are no longer correct. Research on changing fear has highlighted several techniques, most of which rely on the inhibition of the learned fear response. An inherent problem with these inhibition techniques is that the fear commonly returns, for example with stress or even just with the passage of time. I will present research that examines new ways to flexibly control fear and the underlying brain mechanisms. I will describe a brain system mediating various strategies to modulate fear, and present findings suggesting a novel non-invasive technique that could be potentially used to permanently block or even erase fear memories.

Novel optogenetic tools for understanding emergent patterns in neural circuits

Lecture

Date:

Tuesday, January 5, 2010

Hour: 12:30

Location:

Jacob Ziskind Building

Prof. Ofer Yizhar

|

Stanford University, CA

Gamma oscillations are fast (30-80 Hz) rhythmic patterns of neural activity that have been proposed to support information processing in the brain. Gamma rhythms are altered in diseases such as schizophrenia and autism and are therefore of both basic and clinical interest. I have been developing optogenetic tools for light-based control over the activity of genetically defined neuronal populations. A new set of such tools, step function opsins (SFOs), are optimized for modulating the activity of neural circuits and ideal for observing emergent network properties. I will present the molecular engineering approach we used for developing these opsins and show new data on application of these tools to study the mechanisms underlying gamma oscillations in the prefrontal cortex. Some technological aspects will be discussed, with emphasis on the array of available optogenetic tools and how they might be improved to further extend the range of experiments feasible with these new techniques.

Theoretical models of grid cell dynamics and coding in the rat entorhinal cortex

Lecture

Date:

Monday, January 4, 2010

Hour: 11:00

Location:

Nella and Leon Benoziyo Building for Brain Research

Dr. Yoram Burak

|

Center for Brain Science Harvard University

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space, and have been hypothesized to form the neural substrate for dead-reckoning. I will address two theoretical questions that arise from this remarkable experimental discovery: First, how is grid cell dynamics generated in the brain. Second, what information is conveyed in grid cell activity. In discussing the first question, I will focus on continuous-attractor models of grid cell activity, and ask whether such models can generate regular triangular grid responses based on inputs that encode only the rat's velocity and heading direction. In a recent work, we provided a proof of concept that such models can accurately integrate velocity inputs, along trajectories spanning 10-100 meters in length and lasting 1-10 minutes. The range of accurate integration depends on various properties of the continous-attractor network. After presenting these results, I will discuss possible experiments that may differentiate the continuous-attractor model from other proposed models, where activity arises independently in each cell. In the second part of the talk, I will examine the relationship between grid cell firing and rat location, asking what information is present in grid-cell activity about the rat's position. I will argue that, although the periodic response of grid cells may appear wasteful, the grid-cell code is in fact combinatorial in capacity, and allows for unambiguous position representations over ranges vastly larger than the ~0.5-10m periods of individual lattices. Further, the grid cell representation has properties that could facilitate the arithmetic computation involved in position updating during path integration. I will conclude by mentioning some of the implications for downstream readouts, and possible experimental tests.

Sound Texture Perception via Synthesis

Lecture

Date:

Sunday, January 3, 2010

Hour: 14:30

Location:

Nella and Leon Benoziyo Building for Brain Research

Dr. Josh McDermott

|

New York University

Many natural sounds, such as those produced by rainstorms, fires, and swarms of insects, result from large numbers of rapidly occurring acoustic events. Such “sound textures” are often temporally homogeneous, and in many cases do not depend much on the precise arrangement of the component events, suggesting that they might be represented statistically. To test this idea and explore the statistics that might characterize natural sound textures, we designed an algorithm to synthesize sound textures from statistics extracted from real sounds. The algorithm is inspired by those used to synthesize visual textures, in which a set of statistical measurements from a real sound are imposed on a sample of noise. This process is iterated, and converges over time to a sound that obeys the chosen constraints. If the statistics capture the perceptually important properties of the texture in question, the synthesized result ought to sound like the original sound. We tested whether rudimentary statistics computed from the responses of a bank of bandpass filters could produce compelling synthetic textures. Simply matching the marginal statistics (variance, kurtosis) of individual filter responses was generally insufficient to yield good results, but imposing various joint envelope statistics (correlations between bands, and autocorrelations within each band) greatly improved the results, frequently producing synthetic textures that sounded natural and that subjects could reliably recognize. The results suggest that statistical representations could underlie sound texture perception, and that in many cases the auditory system may rely on fairly simple statistics to recognize real world sound textures. Joint work with Andrew Oxenham and Eero Simoncelli.

PKMzeta and the core molecular mechanism of long-term memory storage and erasure

Lecture

Date:

Tuesday, December 29, 2009

Hour: 12:30

Location:

Jacob Ziskind Building

Prof. Todd Sacktor

|

SUNY Downstate Medical Center, Brooklyn, NY

How long-term memories are stored as physical traces in the brain is a fundamental question in neuroscience. Most molecular work on LTP, a widely studied physiological model of memory, has focused on the early signaling events regulating new protein synthesis that mediates initial LTP induction. But what are the newly synthesized proteins that function in LTP maintenance, how do they sustain synaptic potentiation, and do they store long-term memory? Recent studies have identified a brain-specific, autonomously active, atypical PKC isoform, PKMzeta, that is central to the mechanism maintaining the late phase of LTP. In behavioral experiments, the persistent activity of PKMzeta maintains spatial memories in hippocampus, fear-motivated memories in amygdala, and, in work performed in the Dudai lab, elementary associative memories in neocortex. This is because 1-day to several month-old memories appear to be rapidly erased after local intracranial PKMzeta inhibition. PKMzeta, a persistently active enzyme, is thus the first identified molecular component of the long-term memory trace.