A5033877762- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Mitochondrial Function and Pathology
- Physiological and biochemical adaptations
- Plant and Biological Electrophysiology Studies
- Marine Invertebrate Physiology and Ecology
- Lipid Membrane Structure and Behavior
- Cholinesterase and Neurodegenerative Diseases
- Insect and Arachnid Ecology and Behavior
- Neuroendocrine regulation and behavior
- Olfactory and Sensory Function Studies
- Cephalopods and Marine Biology
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Behavioral Health and Interventions
- Protein Kinase Regulation and GTPase Signaling
- Heavy Metal Exposure and Toxicity
- Genetics and Neurodevelopmental Disorders
- Neuroscience, Education and Cognitive Function
- Retinal Development and Disorders
University of Maryland, Baltimore
1998-2022
Society for Neuroscience
2010
University of Pennsylvania
1988-1998
Howard Hughes Medical Institute
1985-1992
Columbia University
1982-1992
New York State Psychiatric Institute
1982-1992
New York State Department of State
1992
Weizmann Institute of Science
1987-1992
New York Psychoanalytic Society and Institute
1983
University of Alberta
1982
A training procedure analogous to differential classical conditioning produces facilitation of excitatory postsynaptic potentials (EPSP's) in the neuronal circuit for siphon withdrawal reflex Aplysia . Thus, tail shock (the unconditioned stimulus) greater monosynaptic EPSP from a sensory neuron motor if is preceded by spike activity than and occur specifically unpaired pattern or occurs alone. Further experiments indicate that this activity-dependent amplification presynaptic origin involves...
We have found that two endogenous neuropeptides in Aplysia, the small cardioactive peptides SCPA and SCPB, facilitate synaptic transmission from siphon mechano-sensory neurons enhance defensive withdrawal reflex these sensory mediate. Single-channel recording revealed close a specific K+ channel, S which is sensitive to cAMP. Moreover, increase cAMP levels neurons. This reduction current slows repolarization of action potential cells, increases transmitter release. In actions, SCPs resemble...
Since the turn of century when basic forms learning were first described by Pavlov and Thorndike, has been divided into two discrete, mutually exclusive, categories—nonassociative associative (see Hilgard Marquis 1940; Razran 1971; Kandel 1976). The categories are distinguished on basis whether requires a specific association between stimuli or stimulus response. most common perhaps interesting comparison nonassociative derives from studies sensitization classical conditioning (see, for...
Presynaptic facilitation of transmitter release contributes to behavioral sensitization and dishabituation, two simple forms learning in Aplysia. This enhancement can be simulated by the facilitatory serotonin has been shown result from types mechanisms. The first facilitating process involves broadening presynaptic action potential sensory neurons reflex is maximally effective when synapse not depressed repeated stimulation, as during sensitization. second independent changes spike duration...
In 1949, D. O. Hebb proposed a novel mechanism for producing changes in the strength of synapses that could account associative learning. According to , synapse might increase when use contributes generation action potentials postsynaptic neuron. Thus, an essential feature this postulate is must occur both cell and presynaptic synaptic occur. We have directly tested 's Aplysia at identified which are known exhibit temporally specific efficacy during cellular analogue differential...
Activity-dependent facilitation is a mechanism of associative synaptic plasticity that contributes to classical conditioning in Aplysia. Previous studies activity-dependent the mechanosensory neurons Aplysia suggested Ca2+ influx during paired spike activity enhances transmitter-stimulated, cAMP-dependent, presynaptic these cells. Moreover, was found potentiate activation adenylate cyclase by transmitter. It therefore proposed Ca2+/calmodulin-sensitive may serve as site interaction between...
Cellular experiments have suggested that during classical conditioning of the gill and siphon withdrawal reflex Aplysia, adenylyl cyclase may serve as a molecular site convergence for Ca2+ serotonin (5-hydroxytryptamine; 5-HT), cellular representations conditioned unconditioned stimuli (CS US). We explored possible basis behavioral requirement CS US be paired within narrow time window in appropriate order. To examine temporal interactions brief pulses 5-HT stimulating Aplysia neural cyclase,...
Facilitation of the monosynaptic connection between siphon sensory neurons and gill motor neuron contributes to sensitization dishabituation withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act parallel increase release from neurons. 5-HT acts, at least partly through cAMP, broaden presynaptic action potential. also a second process facilitates depressed synapses by mechanism independent changes potential duration. Recent experiments...
Enhancement of the defensive withdrawal reflex Aplysia involves a prolongation action potentials mechanosensory neurons, which contributes to facilitation transmitter release from these cells. Recent reports have suggested that whereas cAMP-dependent modulation K+ current increases sensory neuron excitability, cAMP-independent decrease in may increase potential duration and, thus, facilitate release. We tested this proposal using Walsh protein kinase inhibitor or activators cAMP cascade and...
Studies in Aplysia and Drosophila have suggested that Ca2+/calmodulin-sensitive adenylyl cyclase may act as a site of convergence for the cellular representations conditioned stimulus (Ca2+ influx) unconditioned (facilitatory transmitter) during elementary associative learning. This hypothesis predicts rise intracellular free Ca2+ concentration produced by spike activity will cause an increase cyclase. However, published values sensitivity mammals vary widely. The difficulty evaluating...
Grasshoppers, like many poikilotherms, are generally more active at warmer body temperatures. In particular, they jump frequently when warm. To determine the neuronal basis of this increase in jumping activity, we investigated effects temperature on properties identified central neurons known to be involved control jump; these included fast extensor tibiae (FETi) motoneuron and C, G, M interneurons. Heating did not result a reduction current or voltage threshold for action potentials; most...
The Ca2+/calmodulin (CaM)-activated adenylate cyclase has been implicated as playing an important associative role in classical conditioning both Aplysia and Drosophila. Studies of the mammalian cerebral cortex have suggested that Ca2+/CaM sensitivity is confined to a subpopulation total activity. We investigated properties from Aplysia, rat, bovine central nervous system membranes by using CaM-Sepharose chromatography. Although only minority activity bound CaM column, unbound fractions all...
The gastropod mollusk Aplysia is an important model for cellular and molecular neurobiological studies, particularly investigations of mechanisms learning memory. We developed optimized assembly pipeline to generate improved nervous system transcriptome. This transcriptome enabled us explore the evolution cognitive capacity at level. Were there evolutionary expansions neuronal genes between this relatively simple (20,000 neurons) Octopus (500 million neurons), invertebrate with most...
We have characterized paired-pulse facilitation at Aplysia sensory neuron-to-motoneuron synapses. This simple form of very short-term synaptic plasticity displayed an unusual feature: it decreased dramatically with repeated testing. Synaptic depression these synapses and this use-dependent decrease in occurred independently each other. Paired-pulse was inversely correlated the size initial connection absent stronger The same rate large as small synapses, although substantially smaller. Rates...
An important recent insight in a number of neurobiological systems is that during learning, individual dually regulated proteins with associative properties function as critical sites stimulus convergence. During conditioning Aplysia, the Ca2+ /calmodulin-sensitive adenylyl cyclase (AC) mechanosensory neurons serves molecular site interaction between and serotonin [5-hydroxytryptamine (5-HT)]-two signals represent CS US these cells. Conditioning requires be paired within narrow time window...
During short-term sensitization, a simple form of nonassociative learning in Aplysia, the presentation single brief noxious stimulus results enhancement defensive withdrawal reflex lasting minutes to tens minutes. This behavioral plasticity involves presynaptic facilitation synaptic transmission from mechanosensory neurons that mediate their central target cells. is due cAMP-dependent protein phosphorylation. To determine whether time course might be persistent increase activity adenylate...
Calmodulin (CaM)-sensitive adenylyl cyclase (AC) in sensory neurons (SNs) Aplysia has been proposed as a molecular coincidence detector during conditioning. We identified four putative ACs CNS. CaM binds to sequence the C1b region of AC- Apl A that resembles CaM-binding AC1 mammals. Recombinant was stimulated by Ca 2+ /CaM. C is most similar -inhibited AC5 and AC6 directly inhibited , independent CaM. are expressed SNs, whereas B D not. Knockdown demonstrated serotonin stimulation...
The synaptic connections of Aplysia sensory neurons (SNs) undergo dramatic homosynaptic depression (HSD) with only a few low-frequency stimuli. Strong and weak SN synapses, although differing in their probabilities release, HSD at the same rate; this suggests that major mechanism underlying these SNs may not be depletion releasable pool vesicles. In computational models, we evaluated alternative mechanisms HSD, including vesicle depletion, to determine which enable strong synapses depress...
We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) activate adenylyl cyclase (AC) Aplysia CNS. call this class of receptor 5-HT apAC . Eight 14 antagonists tested were against CNS membranes with following rank order potency: methiothepin > metergoline ∼ fluphenazine clozapine cyproheptadine risperidone ritanserin NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone inactive. Methiothepin...