Past events | The department of Brain Sciences

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Optogenetics:Technology Development

Lecture

Date:

Sunday, December 14, 2008

Hour: 14:30

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Prof. Karl Deisseroth

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Depts of Bioengineering& Psychiatry, Stanford University

In 1979, Francis Crick delineated the major challenges facing neuroscience and called for a technology by which all neurons of just one type could be controlled, “leaving the others more or less unaltered”. A new set of technologies now called optogenetics, synthesizing microbial opsins and solid-state optics, has achieved the goal of millisecond-precision bidirectional control of defined cell types in freely behaving mammals. ChR2 was the first microbial opsin brought to neurobiology, where we initially found that ChR2-expressing neurons can fire blue light-triggered action potentials with millisecond precision, as a result of depolarizing cation flux, without addition of chemical cofactors; this approach has since proven versatile across a variety of preparations. Second, in work stimulated by the finding that the all-trans retinal chromophore required by microbial opsins appears already present within mammalian brains, so that no chemical cofactor need be supplied, we found that neurons targeted to express the light-activated chloride pump halorhodopsin from Natronomonas pharaonis (NpHR) can be hyperpolarized and inhibited from firing action potentials when exposed to yellow light in intact tissue and behaving animals; because of the excitation wavelength difference, the two optical gates can be simultaneously used in the same cells even in vivo5. Third, we employed genomic strategies to discover and adapt for neuroscience a third major optogenetic tool, namely a cation channel (VChR1) with action spectrum significantly redshifted relative to ChR2, to allow tests of the combinatorial interaction of cell types in circuit computation or behavior. Fourth, we have developed genetic targeting tools for versatile use of microbial opsins with existing resources including cell type-specific promoter fragments or Cre-LoxP mouse driver lines suitable for a wide variety of neuroscience investigations. Finally, we have developed integrated fiberoptic and solid-state optical approaches to provide the complementary technology to allow specific cell types, even deep within the brain, to be controlled in freely behaving mammals. Prof. Deisseroth is hosted by the students of the Department of Neurobiology, as a part of the departmental students-invited visiting scientist program.

Minerva-Weizmann Workshop on Active Sensing in Touch Vision and Smell

Conference

Date:

Tuesday, December 2, 2008

Hour:

Location:

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As Our Brain Is, So We Are

Lecture

Date:

Monday, December 1, 2008

Hour: 12:15

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Prof. Fred Travis

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Center for Brain, Consciousness, and Cognition Maharishi University of Management, Fairfield, IA

Brain functioning underlies perception of outer objects and supports behavioral responses to environmental challenges. As brain circuits mature in the first 20 years of life, so mental abilities emerge. This talk will examine the relation between brain maturation—synaptogenesis and myelination— and levels of cognitive, moral, and ego development. Learning disabilities, such as ADHD and reading disabilities will be explored in light of associated brain patterns. Effects of experiences on brain functioning will also be examined including effects of restrictive experiences such as stress, drug use and fatigue, and enhancing experiences, such as Transcendental Meditation practice. High levels of human potential will be discussed in terms of enhanced brain functioning.

Role of dopamine systems in addiction

Lecture

Date:

Wednesday, November 26, 2008

Hour: 12:00

Location:

Nella and Leon Benoziyo Building for Brain Research

Prof. Marco Diana

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Laboratory of Cognitive Neuroscience Dept of Drug Sciences, University of Sassari, Italy

Dopamine neurons of the VTA, that project to the Nucleus Accumbens, have been involved in the initial rewarding properties of addicting compounds and, more appropriately, in the long-lasting changes observed after chronic drug administration and subsequent withdrawal. Indeed, alcohol, opiates cannabinoids and other substances provoke, upon withdrawal, a drastic and marked reduction of dopaminergic tone. In addition, aversive, non drug-related stimuli also reduce dopaminergic physiological tone. Furthermore, recent human studies reported an attenuated response to methylphenidate in alcoholic subjects and a lower (than controls) dopaminergic tone. These changes are paralleled by a lower number of D2 receptors and suggest a general “impoverishment” of dopamine transmission in the addicted brain. Accordingly, a dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk. Similar results were reported for nicotine withdrawn rats. This hypodopaminergic state could be the target of therapies aimed at restoring the deficient dopamine transmission observed after chronic drug administration in preclinical and clinical investigations.

Interaction between the amygdala and the prefrontal cortex in emotional memory

Lecture

Date:

Tuesday, November 25, 2008

Hour: 12:30

Location:

Jacob Ziskind Building

Dr. Mouna Maroun

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Department of Neurobiology and Ethology University of Haifa

The amygdala and the medial prefrontal cortex interact to guide emotional behavior. Alterations in the balance between these two structures can lead to persistent fear associations and to the development of anxiety disorders. In this talk I will present work from my laboratory studying the interaction between these two structures in normal conditions and when exposed to a fearful or stressful experience. We have recently found that fear and extinction learning induce differential changes in these two structures that could hint on the mechanisms by which these structures encode memories of fear and safety.

ON THE RELATIONSHIP BETWEEN MOTOR AND PERCEPTUAL BEHAVIOR –

Lecture

Date:

Wednesday, November 12, 2008

Hour: 12:00

Location:

Nella and Leon Benoziyo Building for Brain Research

Dr. Andrei Gorea

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Laboratoire Psychologie de la Perception CNRS & Paris Descartes University

Starting with Goodale & Milner's (1992) neuropsychological observations, a large number of neuropsychological and psychophysical studies has documented a putative dissociation between perception and action. However, a closer inspection of this literature reveals a number of methodological and conceptual shortcomings. I shall present a series of experiments making use of a variety of psychophysical techniques designed to gauge the relationship between Response Times as well Saccade Perturbations and observers' Perceptual States as assessed for not-masked and masked (metacontrast) stimuli via Yes/No, Temporal Order Judgments and Anticipation Response Times paradigms. All these studies reveal a strong action-perceptual state correlation indicating that motor and perceptual responses are based on a unique internal response. A one-path-two-decisions stochastic race model drawing on standard Signal Detection Theory provides a fair account of some of these data, hence overruling the necessity of a two-paths model of visual processing.

New insights into the hallmarks of obsessive-compulsive disorder (OCD): The prevalence of incompleteness and pessimal behavior

Lecture

Date:

Tuesday, November 11, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. David Eilam

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Dept of Zoology, Tel Aviv University

Performance of OCD patients was compared with that of matched normal individuals who were asked to perform the same task that the patients ascribed to their performance. Sequences of consecutive functional acts were long in controls and short in OCD, whereas sequences of non-functional acts were short in controls and long in OCD. Non-functional acts accumulated as a "tail" after the natural termination of the task, supporting the notion of incompleteness as an underling mechanism in OCD. It is suggested that the identified properties are consistent with a recent hypothesis that the individual's attention in OCD shifts from a normal focus on structured actions to a pathological attraction onto the processing of basic acts, a shift that invariably overtaxes memory. Such characteristics and mechanisms of compulsive rituals may prove useful in objective assessment of psychiatric disorders, behavioral therapy, and OCD nosology.

An embedded subnetwork of highly active neurons in the cortex

Lecture

Date:

Wednesday, November 5, 2008

Hour: 14:30

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Dr. Lina Yassin

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Dept of Biological Sciences & Center for the Neural Basis of Cognition Carnegie Mellon University, Pittsburgh, PA

In vivo and in vitro, spontaneous and evoked neuronal activity are sparsely distributed across neocortical networks, where only a small subset of cells show firing rates greater than 1 Hz. Understanding the stability, network connectivity, and functional properties of this active subpopulation has been hampered by an inability to identify and characterize these neurons in vitro. Here we use expression of a fosGFP transgene to identify and characterize the properties of cells with a recent history of elevated activity. Neurons that had induced fosGFP expression in vivo maintained elevated firing rates in vitro over the course of many hours. Paired-cell recordings indicated that fosGFP+ neurons have a greater likelihood of being connected to each other, both directly and indirectly. These findings indicate that highly active neuronal ensembles are maintained over long time periods and suggest that specific, identifiable groups of neurons may dominate the way information is represented in the neocortex.

Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons:

Lecture

Date:

Tuesday, November 4, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Mike Gutnick

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Koret School of Veterinary Medicine The Hebrew University of Jerusalem, Rehovot

CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER

Lecture

Date:

Tuesday, October 28, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Dr. Y. Peng Loh

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Section on Cellular Neurobiology, Program on Developmental Neuroscience, NICHD, NIH, Bethesda

Carboxypeptidase E (CPE) is a prohormone processing enzyme that cleaves C-terminal basic residues from peptide hormone intermediates to yield active hormones, within secretory granules of neuroendocrine cells. A transmembrane form of the enzyme has been shown to be a sorting receptor that sorts prohormones and BDNF at the trans Golgi network and targets them to the regulated secretory pathway. Recently, live cell imaging studies have demonstrated that transport of peptidergic/BDNF secretory vesicles to the release site is dependent upon CPE. The cytoplasmic tail of CPE on the vesicles binds to microtubule motors, KIF1A/KIF3A and dynein via dynactin to effect transport of prohormone/BDNF vesicles in a bidirectional manner from the soma to the process terminals and return. In addition, CPE has been found to play a neuroprotective role in adult brain. In CPE-knockout (KO) mice, degeneration of pyramidal neurons was observed in the hippocampal CA3 region of animals equal or greater than 4 weeks of age, whereas the hippocampus was intact at 3 weeks and younger. Calbindin staining indicated early termination of the mossy fibers before reaching the CA1 region, and a lack of staining of the pyramidal neurons and apical dendritic arborizations in the CA1 region of CPE-KO mice. Ex vivo studies showed that cultured hippocampal neurons transfected with an enzymatically inactive form of CPE were protected against H2O2 oxidative-stress-induced cell death but not in non-transfected or LacZ transfected neurons. Thus CPE has an anti-apoptotic role in the maintenance of survival of adult hippocampal CA3 neurons, although the mechanism of action is unknown. In hepatocellular carcinoma (HCC) cells, overexpression of CPE resulted in enhanced proliferation and migration. SiRNA knockdown of CPE expression in highly metastatic HCC cells inhibited their growth and metastasis in nude mice. These results indicate that CPE is a new mediator of tumor growth and metastasis. Thus CPE is a multi-functional protein which actions include both enzymatic and non-enzymatic to mediate various physiological functions.

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All events, All years

Neural circuits for sensory-guided decisions in rats

Lecture

Date:

Monday, August 4, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Dr. Gidon Felsen

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Cold Spring Harbor Laboratory

We are interested in how the nervous system controls movements based on sensory-cued spatial choices. To this end, we have been studying how rats use olfactory stimuli to select, initiate, execute, and evaluate directional movements. We reasoned that the superior colliculus (SC), a midbrain structure, could play a critical role in these processes, since it is known to be involved in several species in processing sensory input and producing orienting movements. We tested this idea by using tetrodes to record simultaneously from several single neurons in the SC of rats performing a sensory-guided spatial choice task. In this task, an odor cue delivered at a central port determines whether water will be delivered upon entry into the left or right reward port. After sampling the odor, a well-trained rat will, in one fluid movement, withdraw from the odor port, orient left or right, and enter the selected reward port. This task thus requires that a freely moving animal make a spatial choice, while also affording reliable timing of task events and a large number of trials. In this context, not only did a substantial majority of SC neurons encode choice direction during a goal-directed movement, but many also predicted the upcoming choice, maintained selectivity for it after movement completion, or represented the trial outcome. In order to determine whether the observed neural activity is causally related to the movement, we used the GABAA agonist muscimol to unilaterally inactivate the SC in rats performing the spatial choice task. If SC output were necessary for initiating contralateral movements, we would expect inactivation to bias the rat towards ipsilateral choices. Indeed, we found that muscimol, but not saline, biased the rat ipsilaterally, and this bias was dosage-dependent. Our results demonstrate that the SC provides a rich representation of information relevant for several aspects of the control of orienting movements. These representations are necessary for executing appropriate movements. Together, these findings suggest a general role for the SC in behavior requiring sensory-guided navigation.

Hippocampal place field representation of the environment: Encoding, retrieval and remapping

Lecture

Date:

Tuesday, July 29, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Etan Markus

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University of Connecticut

When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. I will present single unit data on examining the issue of how the “hippocampus decides” whether to retrieve an old representation or form a new representation.

Visuo-Motor Mirror Neurons in Human Frontal and Temporal Lobes

Lecture

Date:

Tuesday, July 15, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Dr. Roy Mukamel

|

UCLA

Recently, a unique population of neurons in the monkey ventral pre-motor cortex and in the rostral inferior parietal lobe, have been shown to respond during both execution of a goal-directed action and the perception of a goal-directed action performed by someone else. Since the activity of these motor neurons ‘reflects’ the perceived actions, these neurons have been termed mirror neurons. Due to their unique response properties, these neurons have been implicated in various behaviors such as imitation and empathy. Moreover, a dysfunction of this neural system has been implicated in various disorders such as autism. In humans, there is accumulating evidence from various techniques, supporting the existence of a parallel mirror neuron system however direct evidence is still lacking. We recorded extra-cellular activity of single neurons in medial pre-frontal and medial temporal regions of 23 epileptic patients while performing and observing hand movements and facial gestures. We found that 13.5% of the recorded neurons in both frontal and temporal lobes exhibited visuo-motor mirror properties. A subset of these mirror neurons responded with excitation action-observation and inhibition to action-execution suggesting a possible mechanism for inhibition of unwanted imitation. Our data supports a revision of the current definition of mirror neurons to include not only motor neurons that respond also to the perception of actions performed by others but also perceptual neurons in temporal lobe, responding to actions performed by oneself.

Gateways to tactile perception: Parallel processing of pain and somatosensation

Lecture

Date:

Tuesday, July 8, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Asaf Keller

|

University of Maryland

Vibrissal information is relayed to the barrel cortex through at least two parallel pathways: a lemniscal pathway involving the ventroposterior medial thalamic nucleus (VPM), and a paralemniscal pathway involving the posteromedial nucleus (POm). I will review the role of the lemniscal system, focusing on the mechanisms by which VPM shapes the response properties of neurons in cortical barrels. I will argue that although analyses of these properties (e.g. receptive field structure and angular preference) have illuminated the process of input transformation in sensory pathways, they may have only limited ethological role. I will show that this lemniscal pathway is critical for temporal coding of somatosensory inputs. In the paralemniscal pathway, and in POm in particular, neurons respond poorly and unreliably to physiologically relevant stimuli. I will show that the GABAergic nucleus zona incerta (ZI) regulates POm activity is a state-dependent manner. This regulation is mediated by the cholinergic activating system, which enhances POm activity during states of arousal and vigilance. However, even in these states, POm neurons fail to reliably encode sensory inputs. I will show that POm is critically involved in coding noxious stimuli. Specifically, I will present evidence in support of the hypothesis that the phenomenon of central pain may be the result of suppressed inhibitory regulation of POm activity.

DC Magnetic Fields Produced by the Human Body

Lecture

Date:

Thursday, July 3, 2008

Hour: 15:00

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Prof. David Cohen

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Biomag Group Leader (ret.), MIT Magnet Lab,& Assoc. Prof. of Radiology, Harvard Med. School

This is a review of measurements made mostly at the MIT Biomag Lab during the period of 1969 to 1983, partly in collaboration with Prof. Yoram Palti. These measurements are usually unique, in that their current sources are difficult to be seen with electric potentials. They are timely today because the new multi-channel SQUID systems are now being made capable of measuring DC fields from the head (and other organs). Our measurements were essentially a mapping over the whole body. DC fields were found almost everywhere, from many internal sources. They were larger over the limbs and head than over the torso proper, except over the abdomen, where it was largest. Over the head, there were puzzling signals from vicinity of healthy hair follicles, suggesting that so-called neural sources of the dcMEG could be overshadowed by more superficial sources. One major mechanism for generating these fields generally appeared to be a change in the K+ concentration in the vicinity of long excitable fibers. Overall, we concluded that DC fields are a rich and complex phenomena, including the dcMEG.

Information theory and the perception-action-cycle

Lecture

Date:

Tuesday, July 1, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Naftali Tishby

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School of Computer Science & Engineering and Interdisciplinary Center for Neural Computation The Hebrew University, Jerusalem

I will argue that living organisms can be characterized by their abilities to exchange information with their environment through sensing and acting. Moreover, the optimal interaction of an organism with its environment is determined by the information it can extract and store from the past about the future of its environment, on multiple time scales. Its optimal achievable performance is therefore bounded by the predictive-information of the environment, in some analogy with the entropy and channel-capacity bounds in Shannon's theory of communication. In that sense, life utilizes the predictability of its environment and act in order to increase its predictive capacity. This conceptual and quantitative framework can allow us to design and analyze experiments in neuroscience in a new way. I will discuss some recent applications to auditory and motor physiology.

Wiring mechanisms in the mammalian somatosensory system

Lecture

Date:

Tuesday, June 24, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Avraham Yaron

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Dept of Biological Chemistry, WIS

During development, the basic wiring of the nervous system is established by connecting trillions of neurons to their target cells. To reach their correct targets, neurons extend axons that are guided by cues in the extracellular environment. The talk will describe our efforts to understand the mechanisms of axonal guidance using the somatosensory system as a model; with special focus on the role of the Semaphorins family of guidance cues in the process.

Grouping by synchrony and precise temporal patterns in the visual cortex: evidence from voltage-sensitive dye imaging

Lecture

Date:

Sunday, June 22, 2008

Hour: 10:00

Location:

Arthur and Rochelle Belfer Building for Biomedical Research

Dr. Hamutal Slovin

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Bar Ilan University

Accumulating psychophysical and physiological evidence suggest the involvement of early visual areas in the process of visual integration and specifically in local facilitation of proximal and collinear stimuli. To investigate the early integration mechanisms at the population level, we performed voltage-sensitive dye imaging that is highly sensitive to subthreshold population activity, and imaged from the primary visual cortex (V1) and extrastriate cortex (V2) of a behaving monkey. The animal was trained on a simple fixation task while presented with collinear or non-collinear patterns of small gratings, Gabors or short oriented bars. Facilitation in terms of increased amplitude activity at the corresponding retinotopic site of the target was observed for low contrast targets presented as part of collinear or non-collinear pattern. The facilitation effect and its time course depended on the target flanker separation distance, suggesting the role of horizontal connections. Next, we compared the dynamics of cortical response. We found that the time course of responses increased faster in the collinear pattern as compared with the non-collinear pattern. Finally, to study synchronization, we calculated the spatial correlation of pixels at the target location and found that correlation was higher for the collinear pattern, suggesting that the neuronal code for collinear versus non-collinear pattern may be carried by synchronization and response dynamics rather than simply maximal amplitude of response. These results suggest that neuronal population activity in area V1 is involved in local visual integration processes, and specifically in the increased sensitivity for low-contrast visual stimuli surrounded by high contrast flankers. In the second part of my talk I will discuss repeating spatio-precise spatio-temporal patterns. Numerous studies of neuronal coding have reported precise time relations among spikes in cortical neurons. Here our main goal was to study whether information processing in the cortex involves precise spatio-temporal patterns and to detect and characterize those patterns among neuronal populations exploiting voltage-sensitive dye imaging (VSDI) in visual cortical areas of a fixating monkey. Our preliminary results demonstrate that spatio-temporal patterns do exist above chance level (p<0.0001). The spatial characteristics of those patterns are consistent with physiological studies regarding the interplay between different visual areas, and the temporal characteristics show that the majority of the patterns appear in a range of 10-20ms apart

Timing and the olivo-cerebellar system

Lecture

Date:

Tuesday, June 17, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Prof. Yosef Yarom

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Hebrew University of Jerusalem

The crystal-like anatomy and circuitry of the cerebellum and its preservation throughout vertebrate phylogeny suggest that it performs a single basic computation. It has been proposed that this basic computation is to create temporal patterns of activity necessary for timing motor, sensory and cognitive tasks. Despite the wide agreement about the involvement of the cerebellum in temporal coordination, there is an ongoing debate as to the neural mechanism that subserves this function. This debate stems from the current dogma that dominates cerebellar research. According to this dogma, PC simple spikes are evoked by input from granule cells and determine cerebellar nuclear (CN) activity, thus governing cerebellar output. The complex spikes, according to this view, serve as an error signal which is used by the system to readjust the simple spike activity. A novel theory of cerebellar function will be presented. According to this theory, the complex spike, rather than the simple spike, transmits the cerebellar output. The inferior olive generates accurate temporal patterns orchestrated by the cerebellar cortex and implemented in a variety of motor and non-motor tasks. Although this is a radical change of concept, it is well supported by experimental observations and it settles major problems inherent to the current dogma

Incubation of cocaine craving: behavioral and neuronal mechanisms

Lecture

Date:

Tuesday, June 10, 2008

Hour: 12:15

Location:

Jacob Ziskind Building

Dr. Yavin Shaham

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National Institute on Drug Abuse, NIH

Abstract: Using a rat model of drug relapse and craving, we previously found time-dependent increases in cocaine seeking induced by exposure to drug cues after withdrawal from the drug, suggesting that cocaine craving incubates over time. In this lecture, I will first summarize our earlier behavioral and neurophysiological studies on incubation of cocaine craving. I will then discuss in more detail results from more recent studies implicating neuronal activity in the ventromedial prefrontal cortex and glutamate synaptic plasticity in the nucleus accumbens in the incubation of cocaine craving. I will also briefly address the relevance of our rat findings to the understanding of relapse to drug use in humans. Selected references related to incubation of cocaine craving Grimm JW, Hope B, Wise RA, Shaham Y (2001) Incubation of cocaine craving after withdrawal. Nature 412:141-142 Grimm JW, Lu L, Hayashi T, Su TP, Hope BT, Shaham Y (2003) Time dependent increases in brain-derived neurotrophic factor (BDNF) protein levels within the mesolimbic dopamine system following withdrawal from cocaine: implications for incubation of cocaine craving. The Journal of Neuroscience 23:742-747 Lu L, Dempsey J, Liu S, Bossert J, Shaham Y (2004) A single infusion of BDNF into the ventral tegmental area induces long-lasting potentiation of cocaine-seeking after withdrawal. The Journal of Neuroscience 24:1604-1611 Lu L, Grimm JW, Hope BT, Shaham Y (2004) Incubation of cocaine craving after withdrawal: a review of preclinical data. Neuropharmacology 47(S1): 214-227 (invited review for a special issue commemorating 30 years of NIDA research) Lu L, Hope BT, Dempsey J, Liu S, Bossert JM, Shaham Y (2005) Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nature Neuroscience 8:212-219 Shaham Y, Hope BT (2005) The role of neuroadaptations in relapse to drug seeking. Nature Neuroscience 8:1437-1439 (special issue on Neurobiology of Addiction) Lu L, Uejima JL, Gray SM, Bossert JM, Shaham Y (2007) Systemic and central amygdala injections of the mGluR2/3 agonist LY379268 attenuate the expression of incubation of cocaine craving. Biological Psychiatry 61:591-598 Koya E, Uejima J, Wihbey K, Bossert JM, Hope BT, Shaham Y (2008) Role of ventral medial prefrontal cortex in incubation of cocaine craving. Neuropharmacology (in press, for a special issue commemorating 35 years of NIDA research)) Conrad KL, Tseng K, Uejima J, Reimers J, Heng L, Shaham Y, Marinelli M, Wolf ME (2008) Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature (in press)