Cerebellar-Dependent Learning in Larval Zebrafish

Understanding how neuronal network activity contributes to memory formation is challenged by the complexity of most brain circuits and the restricted ability to monitor the activity of neuronal populations in vivo. The developing zebrafish (Danio rerio) is an animal model that circumvents these problems, because zebrafish larvae possess a rich behavioral repertoire and an accessible brain. Here, we developed a classical conditioning paradigm in which 6- to 8-d-old larvae develop an enhanced motor response to a visual stimulus (conditioned stimulus, CS) when it is paired with touch (unconditioned stimulus, US). Using in vivo calcium imaging we demonstrate that CS and US activate different subsets of neurons in the cerebellum; their activity, modulated by learning two-photon laser ablation, revealed that the cerebellum is involved in acquisition and extinction, but not the retention, of this memory

Protein synthesis at synaptic sites on dendrites

Studies over the past 20 years have revealed that gene expression in neurons is carried out by a distributed network of translational machinery. One component of this network is localized in dendrites, where polyribosomes and associated membranous elements are positioned beneath synapses and translate a particular population of dendritic mRNAs. The localization of translation machinery and mRNAs at synapses endows individual synapses with the capability to independently control synaptic strength through the local synthesis of proteins. The present review discusses recent studies linking synaptic plasticity to dendritic protein synthesis and mRNA trafficking and considers how these processes are regulated. We summarize recent information about how synaptic signaling is coupled to local translation and to the delivery of newly transcribed mRNAs to activated synaptic sites and how local translation may play a role in activity-dependent synaptic modification

Nitric oxide and synaptic function

The free radical gas nitric oxide (NO) is a recently identified neuronal messenger that carries out diverse signaling tasks in both the central and peripheral nervous systems. Whereas most neurotransmitters are packaged in synaptic vesicles and secreted in a Ca2+-dependent manner from specialized nerve endings, NO is an unconventional transmitter which is not packaged in vesicles, but rather diffuses from its site of production in the absence of any specialized release machinery. The lack of a requirement for release apparatus raises the possibility that NO can be released from both pre- and postsynaptic neuronal elements. In addition, because NO is gaseous and extremely membrane permeant, it can bypass normal signal transduction routes involving interactions with synaptic membrane receptors. Although the targets of NO have not yet been completely described, it is known that NO can bind to the iron contained in heine groups, leading to conformational changes in associated proteins, such as guanylyl cyclase

Further analysis of the effects of baffles on combustion instability

A computerized analytical model, developed to predict the effects of baffles on combustion instability, was modified in an effort to improve the ability to properly predict stability effects. The model was modified: (1) to replace a single spatially-averaged response factor by separate values for each baffle compartment; (2) to calculate the axial component of the acoustic energy flux, and (3) to permit analysis of traveling waves in a thin annular chamber. Allowance for separate average response factors in each baffle compartment was found to significantly affect the predicted results. With this modification, an optimum baffle length was predicted which gave maximum stability

Activity of human hippocampal and amygdala neurons during retrieval of declarative memories

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning

Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase

Operating manual for coaxial injection combustion model

An operating manual for the coaxial injection combustion model (CICM) is presented as the final report for an eleven month effort designed to provide improvement, to verify, and to document the comprehensive computer program for analyzing the performance of thrust chamber operation with gas/liquid coaxial jet injection. The effort culminated in delivery of an operation FORTRAN IV computer program and associated documentation pertaining to the combustion conditions in the space shuttle main engine. The computer program is structured for compatibility with the standardized Joint Army-Navy-NASA-Air Force (JANNAF) performance evaluation procedure. Use of the CICM in conjunction with the JANNAF procedure allows the analysis of engine systems using coaxial gas/liquid injection