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Perception and Action Interactions:Evidence from Neuropsychology, Neuroimaging, and Transcranial Magnetic Stimulation
Lecture
Thursday, March 26, 2009
Hour: 11:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Perception and Action Interactions:Evidence from Neuropsychology, Neuroimaging, and Transcranial Magnetic Stimulation
Prof. Jody Culham
Dept of Psychology, University of Western Ontario, Canada
Visiting Senior Fellow, Institute of Advanced Studies
University of Bologna, Italy
Although prominent theories of vision have emphasized dissociations between two visual streams specialized for perception and action, in some situations, the two streams must interact. One such situation is the performance of actions upon remembered objects. Neuropsychological evidence from two patients with occipitotemporal lesions suggests that while immediate actions can be performed using only the dorsal vision-for-action stream, delayed actions require integrity of the ventral vision-for-perception stream. My lab has investigated the interactions between the two streams during delayed grasping using functional magnetic resonance imaging and transcranial magnetic stimulation. Our results suggest that delayed actions re-recruit information about object properties such as shape, size and orientation from the ventral stream and early visual areas at the time the delayed action is performed
Synergistic Interactions Between Molecular Risk Factors of Alzheimer’s Disease
Lecture
Tuesday, March 24, 2009
Hour: 12:30
Location:
Jacob Ziskind Building
Synergistic Interactions Between Molecular Risk Factors of Alzheimer’s Disease
Prof. Daniel Michaelson
Dept of Neurobiology,
Tel Aviv University
The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer’s disease, is associated with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated via synergistic pathological interactions with amyloid β (Aβ). We have recently shown that activation of the amyloid cascade by inhibition of the Aβ-degrading enzyme neprilysin in brains of apoE3 and apoE4 mice results in the isoform specific degeneration in apoE4 mice, of hippocampal CA1 neurons and of entorhinal and septal neurons. This is accompanied by the accumulation of intracellular Aβ and apoE and by pronounced cognitive deficits in the ApoE4 mice. We presently investigated the cellular mechanisms underlying the apoE4 dependent Aβ mediated neurodegeneration of CA1 and septal neurons and their neuronal specificity. Confocal microscopy kinetic studies revealed that the accumulated Aβ in CA1 neurons of apoE4 mice co-localizes with lysosomes and is associated with lysosomal activation and subsequent apoptotic neuronal cell death. Furthermore the accumulated Aβ is oligomerized. In contrast the degeneration of septal neurons is not associated with oligomerization of the accumulated Aβ. Instead intracellular Aβ in septal neurons co-localizes with the apoE receptor LRP whose levels are specifically elevated in these cells. These findings suggest that the apoE4 dependent Aβ mediated neurodegeneration is related, in CA1 but not in septal neurons, to oligomerization of the accumulated Aβ. In addition, neurodegeneration of CA1 but not of septal neurons is associated with inflammatory activation suggesting that the brain area specificity of the effects of apoE4 and Aβ are also related to brain area specific non neuronal mechanisms such as inflammation.
Neuronal plasticity experiments revealed that apoE4 inhibits synaptogenesis and neurogenesis and stimulates apoptosis in hippocampal neurons of apoE4 mice that have been exposed to an enriched environment. These effects are also associated with the specific accumulation of apoE4 and oligomerized Aβ in the affected neurons. Additional experiments revealed that apoE4 up-regulates the expression of inflammation-related genes following i.c.v injection of LPS and that this effect is also associated with the accumulation of intra neuronal Aβ in hippocampal neurons. These findings suggest that the impaired neuronal plasticity and hyper inflammatory effects of apoE4 may also be mediated via cross talk interactions of apoE4 with the amyloid cascade.
Now I See It, Now I Don’t: Neural Basis of Simple Perceptual Decisions in the Human Brain
Lecture
Wednesday, March 18, 2009
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Now I See It, Now I Don’t: Neural Basis of Simple Perceptual Decisions in the Human Brain
Dr. Tobias H. Donner
Center for Neural Science & Dept of Psychology
New York University
It is frequently proposed that conscious perceptual decisions are produced by recurrent interactions among multiple brain areas. Sensory stimuli, which are close to psychophysical threshold or perceptually bistable, induce fluctuating percepts in the face of constant sensory input. Thus, these stimuli provide ideal tools for probing the intrinsic neural mechanisms underlying perceptual decisions, in the absence of extrinsic stimulus changes. I will present human neuroimaging (MEG and fMRI) studies, in which we used this approach for probing the large-scale neural mechanisms underlying decisions about the presence or absence of simple visual features. Our results suggest that neural population activity in parietal, prefrontal, and premotor areas reflects the decision process, and that population activity in extrastriate ventral visual cortex reflects perception. Further, cooperative and competitive long- range interactions, across multiple levels of the cortical processing hierarchy, both seem to underlie simple perceptual decisions.
How circadian clocks keep time: insights from Drosophila
Lecture
Tuesday, March 17, 2009
Hour: 12:30
Location:
Jacob Ziskind Building
How circadian clocks keep time: insights from Drosophila
Dr. Sebastian Kadener
Dept of Biological Chemistry
The Hebrew University of Jerusalem
Circadian rhythms in locomotor activity are an example of a well-characterized behavior for which the molecular and neurobiological bases are not yet completely understood. These rhythms are self-sustained 24 hours rhythms that underlie most physiological and behavioral processes. The central circadian clock, which is situated in the brain, is responsible for daily rhythms in locomotor activity that persist even after weeks in constant darkness (DD). Peripheral clocks are spread trough the fly body and regulate a plethora of physiological functions that include: olfaction, detoxification and immunity. All these clocks keep time trough complex transcriptional-translational feedback loops that include the proteins CLK, CYC, PER and TIM. My research focuses on the study of the molecular basis of the circadian clock. In particular, I am interested in the contribution of the different molecular interactions and processes to the generation of robust 24hs rhythms. In this context, I have recently demonstrated that transcriptional speed of the clock gene PER is a determinant of the circadian period and that translational regulation by miRNAs is part of the central circadian clock.
Complex Translational Control in the Gustatory Cortex Determines the Stability of a Taste Memory
Lecture
Thursday, March 12, 2009
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Complex Translational Control in the Gustatory Cortex Determines the Stability of a Taste Memory
Dr. Kobi Rosenblum
Dept of Neurobiology, University of Haifa
The off-line processing of acquired sensory information in the mammalian cortex is an example for the unique way biology creates to compute and store information which guides behavior. The relatively short temporal phase in the process (i.e. hours following acquisition) is defined biochemically by its sensitivity to protein synthesis inhibitors. Until recently this negative definition of molecular consolidation did not reveal the details of the endogenous processes taking place, minutes to hours, in the neurons and circuit underlying a given memory. We use taste learning paradigms in order to study this process of molecular consolidation in the gustatory cortex.
Recent results, from our laboratory, obtained from genetic, pharmacological, biochemical, electrophysiological and behavioral studies demonstrate that translational control, at the initiation and elongation phases of translation, plays a key role in the process of molecular consolidation. Moreover, this spatially and temporally regulated translation control modifies both general and synaptic protein expression that is crucial for memory stabilization. We propose a model to explain the interplay between regulation of initiation and elongation phases of translation and demonstrate that in certain situations cognitive enhancement can be achieved.
Unravelling signal processing in the cortical column
Lecture
Tuesday, February 24, 2009
Hour: 12:30
Location:
Jacob Ziskind Building
Unravelling signal processing in the cortical column
Prof. Idan Segev
Department of Neurobiology &
Interdisciplinary Center for Neural Computation
Hebrew University, Jerusalem
Never before have such intense experimental efforts been focused on neuronal circuits of the size of few hundred thousands neurons whose functions are relatively well defined. The extraordinarily powerful new genetic tools and 3D reconstruction methods, combined with modern multi-electrode arrays, telemetry, two-photon imaging and photo-activation are starting to shed bright light on the intricacies of these circuits, and in particular of the cortical column. But without tools that integrate all this different types of data, one cannot expect to gain a comprehensive understanding on how these circuits perform specific sensory-motor or cognitive functions. As in any other complex system, a modeling study is essential if we are to ever say that we understand how this system works. I will describe several attempts in my group to begin building detailed models of the cortical column, highlighting that, at both circuit level and at the level of individual neurons, models should capture experimental variability and that the building of these models should become automated. I will demonstrate how these models could be used to fruitfully guide new experiments and discuss were all this new integrated "simulation-driven brain research agenda" might lead to.
“Intersectional Optogenetics" unearths neurons that drive fish locomotion
Lecture
Wednesday, February 18, 2009
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
“Intersectional Optogenetics" unearths neurons that drive fish locomotion
Prof. Ehud Isacoff
Dept of Molecular & Cell Biology
UC Berkeley
A major challenge for biology is to develop new ways of determining how proteins operate in complexes in cells. This requires molecularly focused methods for dynamic interrogation and manipulation. An attractive approach is to use light as both input and output to probe molecular machines in cells. While there has been significant progress in optical detection of protein function, little advance has been made in remote control of any kind, including optical methods. As part of our efforts in the NIH Nanomedicine Development Center for the Optical Control of Biological Function, we are developing methods for rapidly switching on and off with light the function of select proteins in cells. The strategies are broadly applicable across protein classes.
Our approach has been to synthesize Photoswitched Tethered Ligands (PTLs), which are attached in a site directed manner to a protein of interest. The site of attachment is designed into the protein to be at a precise distance from a binding site for the ligand. The geometric precision has two important consequences. First, light of two different wavelengths is used to isomerize the linker in such a way that the ligand can only bind in one of the sites, thus making it possible to toggle binding on and off with light. Second, native proteins are not affected by the PTL and remain insensitive to light, since the PTL does not attach. This means that a specific protein in a cell, a tissue and even in an intact freely behaving organism, can have its biochemical signaling turned on and off by remote optical control. The switching is very fast, taking place in ~1 millisecond, i.e. at the rate of the fastest nerve impulse.
I will describe how we used our light-gated kaintate-type glutamate receptor, LiGluR, to study vertebrate locomotion. We used intersectional optogenetics in larval zebrafish to identify a new class of neurons that provide an important modulatory drive to swim behavior.
Computing as modeling
Lecture
Tuesday, February 17, 2009
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Computing as modeling
Prof. Oron Shagrir
Dept of Philosophy & Dept of Cognitive Science
Hebrew University, Jerusalem
The view that the brain computes is a working hypothesis in cognitive and brain sciences. But what does it mean to say that a system computes? What distinguishes computing systems, such as brains, from non-computing systems, such as stomachs and tornadoes? I argue that a "structural" approach to computing cannot account for much of the computational work in cognitive neuroscience. Instead, I offer a modeling account, which is a variant of a "semantic" approach. On this modeling account, the key feature of computing is a similarity between the "inner" mathematical relations, defined over the representing states, and "outer" mathematical relations, defined over the represented states.
Changes in the brain during chronic nicotine: from thermodynamics to neuroadaptation
Lecture
Tuesday, February 17, 2009
Hour: 10:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Changes in the brain during chronic nicotine: from thermodynamics to neuroadaptation
Prof. Henry Lester
California Institute of Technology
The Development of Reading Pathways in School Age Children
Lecture
Thursday, February 12, 2009
Hour: 11:30
Location:
Nella and Leon Benoziyo Building for Brain Research
The Development of Reading Pathways in School Age Children
Dr. Michal Ben-Shachar
English Dept and the Gonda Brain Research Center
Bar Ilan University
Learning to read involves exposure to large amounts of print in a focused period of time during childhood. How does this environmental transition affect cortical circuits for visual perception and shape recognition? I will present data from a developmental study of reading examining the relation between reading skill, cortical function and white matter properties in school age children. Functional properties in area MT+, and white matter properties in temporal callosal fibers, are both correlated with reading skill. I will discuss possible interpretations of these findings within a general model of the reading pathways.
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ON THE RELATIONSHIP BETWEEN MOTOR AND PERCEPTUAL BEHAVIOR –
Lecture
Wednesday, November 12, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
ON THE RELATIONSHIP BETWEEN MOTOR AND PERCEPTUAL BEHAVIOR –
Dr. Andrei Gorea
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
Tuesday, November 11, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
New insights into the hallmarks of obsessive-compulsive disorder (OCD): The prevalence of incompleteness and pessimal behavior
Prof. David Eilam
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
Wednesday, November 5, 2008
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
An embedded subnetwork of highly active neurons in the cortex
Dr. Lina Yassin
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
Tuesday, November 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons:
Prof. Mike Gutnick
Koret School of Veterinary Medicine
The Hebrew University of Jerusalem, Rehovot
CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER
Lecture
Tuesday, October 28, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER
Dr. Y. Peng Loh
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.
Population imaging in vivo: from the awake to the anesthetized
Lecture
Tuesday, October 7, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Population imaging in vivo: from the awake to the anesthetized
Prof. Jason Kerr
Max Planck Institute, Tubingen, Germany
It is unclear how the complex spatiotemporal organization of ongoing cortical neuronal activity recorded in anesthetized animals relates to the awake animal. We therefore used two-photon population calcium imaging in awake and subsequently anesthetized rats to follow action potential firing in populations of neurons across brain states, and examined how single neurons contributed to population activity. Firing rates and spike bursting in awake rats were higher, and pair-wise correlations were lower, compared with anesthetized rats. Anesthesia modulated population-wide synchronization and the relationship between firing rate and correlation. Overall, brain activity during wakefulness cannot be inferred using anesthesia.
Decoding conscious and unconscious mental states from brain activity in humans
Lecture
Tuesday, September 23, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Decoding conscious and unconscious mental states from brain activity in humans
Prof. Dr. John-Dylan Haynes
Bernstein Center for Computational Neuroscience, Charité Berlin &
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Recent advances in human neuroimaging have shown that it is possible to accurately read out a person's conscious experience based only on non-invasive fMRI measurements of their brain activity. This "brain reading" is possible because each thought is associated with a unique pattern of brain activity that can serve as a "fingerprint" of this thought in the brain. By training a computer to recognize these fMRI "thought patterns" it is possible to read out what someone is currently thinking with high accuracy. Here several studies will be presented that also directly address the relationship between neural encoding of information (as measured with fMRI) and its availability for awareness. These studies include comparisons of neural and perceptual information, unconscious information processing, decoding of time courses of perception, as well as decoding of high-level mental states. This will show that it is possible to read out a person's concealed intentions and even to predict how someone is going to decide a few seconds later. Finally, the talk will discuss fundamental challenges and limitations of the field, along with the ethical question if such methods might one day be a danger to our mental privacy.
Comparing spontaneous and stimulus-evoked activities in human sensory cortex
Lecture
Tuesday, September 16, 2008
Hour: 12:15
Location:
Nella and Leon Benoziyo Building for Brain Research
Comparing spontaneous and stimulus-evoked activities in human sensory cortex
Yuval Nir (Rafi Malach Group)
Department of Neurobiology, WIS
Traditionally, the brain and sensory cortex in particular have been viewed as being primarily driven by external events, but recent studies in anesthetized animals revealed robust spontaneous activity in sensory cortex, highlighting the intrinsic nature of brain processing. Using fMRI we found widespread slow fluctuations occurring spontaneously in the human visual cortex in the absence of external stimuli. These waves exhibited a consistent and specific neuro-anatomical distribution, suggesting that they largely reflect neuronal activity rather than hemodynamic noise sources. In further studies we obtained neurophysiological recordings in neurosurgical patients, and found direct electrophysiological evidence for such slow spontaneous neuronal fluctuation in human sensory cortex. These fluctuations were evident mainly in neuronal firing rates and in LFP gamma power changes, showed unique temporal dynamics following 1/f power laws, and were found to be correlated between corresponding ‘mirror’ sites across hemispheres within specific functional networks. Overall, these results extend previous animal studies of spontaneous activity by revealing and characterizing such activity in human sensory cortex.
Strong Loops in the Neocortex
Lecture
Wednesday, August 13, 2008
Hour: 12:15
Location:
Wolfson Building for Biological Research
Strong Loops in the Neocortex
Prof. Henry Kennedy
Dept of Integrative Neuroscience
INSERM, France
Hierarchy provides a major conceptual framework for understanding structure-function relationships of the cortex (Felleman and Van Essen, Cerb Cortex 1991). Feedforward (rostral directed) projections link areas in an ascending series and have a driving influence; feedback (caudal directed) projections link areas in a descending series and have a modulatory influence. This has led to the suggestion that feedforward projections are uniquely reciprocated by feedback projections i.e no strong loops (Crick and Koch, Nature 1998). We have re-examined this issue by making retrograde tracer injections in 22 areas spanning the occipital, parietal, temporal and frontal lobes. Injections were placed in areas V1, V2, V4 TEO, STPa, STPm, STPp, AudPba, AudPbp, 5, 7a, 7b, F1, 2, 8a, 45b, 9/46d, 9/46v, 46d, F5, ProM, 24c. High frequency sampling allows determination of indices of laminar distribution (SLN) and the relative strength (FLN) of connections (Vezoli et al., The Neuroscientist 2004). Analysis shows an inverse relationship between strength of connection and distance and revealed many (30%) hitherto unknown long-distance connections. Elsewhere we have shown that cortico-cortical projections form a smooth gradient: long-distance ascending connections are strongly feedforward (high SLN XX 100%) and on approaching the injection site have progressively lower SLN values (reaching 51%); likewise long-distance descending connections are strongly feedback (low SLN XX 0) and approaching the injection site reduce SLN 49% (Barone and Kennedy, J. Neurosci. 2000). The Felleman and Van Essen data is strictly hierarchical (no strong loops). A topological model of our data shows small world features (high cluster index and short average path distances) and five strong loops. Strong loops link frontal areas with occipital (areas 45-V4, 8A-V4), temporal (areas 45-TEO, 46-TEO) and parietal (areas 8A-7A, 46-7A) areas. The areas participating in strong loops exhibit high degrees of connectivity and constitute the hubs promoting small world attributes in the cortical architecture. The strong loops make it possible to go from V4 to all higher areas and back to V4 by uniqely feedforward pathways in an average of 3 and a maximum of 8 steps. One consequence of these anti-hierarchical connections is that the computations carried out in the supragranular layers of the cortex (Douglas and Martin, Annual Rev Neurosci. 2004) can be widely distributed in large-scale cortical networks mediating top-down control.
Extended Access to Self-Administered Cocaine –A Model for Cocaine Addiction
Lecture
Tuesday, August 12, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Extended Access to Self-Administered Cocaine –A Model for Cocaine Addiction
Dr. Osnat Ben-Shahar
Dept of Psychology
University of California Santa Barbara
Animal models used to study neuronal mechanisms of drug addiction most commonly rely upon either repeated experimenter-administered cocaine or drug-administration protocols that result in stable patterns of drug-taking. However, it is well established that differences in the route of administration (IV vs. IP or SC) and in the control over administration (self-administered vs. experimenter-administered) lead to differences in cocaine-induced neurochemical effects. In addition, the neural consequences of cocaine administration are different when tested in the middle of the administration protocol, immediately after the last administration of cocaine, or after 2, 14 or 60 days of withdrawal. Finally, the frequency and size of the daily-dose of cocaine are important factors determining the nature of the changes induced by cocaine. It would seem, then, that if we are to better understand the neuroadaptations that underlie the development of addiction in humans, animal models that mimic as closely as possible the human situation should be employed. Hence, my lab uses an animal model that employs an IV route of administration (as opposed to IP or SC), requiring self-administration (as opposed to experimenter-administered), under conditions (based on Ahmed & Koob, 1998) that distinguish the effects of short versus extended daily access to cocaine upon both behavior and neural substrates. This permits the investigation of neuroadaptations associated with the transition from the drug-naïve state to controlled drug-use, versus the further adaptations associated with the transition from controlled to compulsive drug-use. The differences we found, in both behavior and underlying neuronal adaptations, between controlled and compulsive drug-states, will be discussed in this talk.
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