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C A Barnes

Publications and source records attributed to C A Barnes.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat.

The current study dissected the fascia dentata (FD) and hilar region from the CA and subicular cell fields of the rat and conducted in vitro determinations of the number of binding sites for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) glutamate receptors across the lifespan. We determined the density of binding of [3H]-glutamate or [3H]-AMPA to NMDA or AMPA receptor sites, respectively. The changes reported might be due to either a change in receptor number or an alteration in the binding characteristics of the receptor site with aging. We found an age-related decline in the number of NMDA receptors in the CA1, CA3 and subicular cell regions of the hippocampus, but not in the FD/hilar region, and an age-related decline in the number of AMPA receptors in the FD/hilar region, but not in the CA fields. The decline in the number of NMDA or AMPA receptors that occurs with aging was not a continuous or homogeneous process. These changes in receptor number might underlie selected age-associated changes in sensitivity to drugs that influence hippocampal function as well as to changes in NMDA-dependent long-term potentiation. A thorough understanding of the mechanisms underlying changes in glutamate receptor function in discrete brain regions, using combined neurochemical and electrophysiological methods, may ultimately provide insight into the fundamental substrates of age-associated memory disorders related to hippocampal dysfunction.

Aging↗
PubMed2000

Effect of age on burst firing characteristics of rat hippocampal pyramidal cells.

During behavior, hippocampal pyramidal cells emit high frequency bursts, modulated by the animal's location and the 7 Hz theta rhythm. During rest, CA1 EEG exhibits large irregular activity (LIA), containing sharp-wave/ripple complexes, during which pyramidal cells exhibit burst discharge. Aging results in altered intracellular calcium homeostasis, increased electrical coupling and reduced cholinergic modulation within CA1, all of which might affect burst discharge characteristics. During LIA, old rats exhibited more short (3-7 ms) inter-spike intervals, with no change in mean firing rate. During behavior induced theta rhythm, however, interval distributions were not affected by age. Thus, different mechanisms must underlie burst discharge in theta and LIA states. Moreover, age related changes in the cholinergic system appear not to play a major role in shaping the temporal discharge characteristics of CA1 pyramidal cells. The mechanism and significance of the higher frequency bursting in old rats during LIA remains to be determined.

Aging↗
PubMed2000

Regulation of T cell activation, anxiety, and male aggression by RGS2.

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Galpha protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes after activation. To investigate the role of RGS2 in vivo, we generated rgs2-deficient mice. We show that targeted mutation of rgs2 in mice leads to reduced T cell proliferation and IL-2 production, which translates in an impaired antiviral immunity in vivo. Interestingly, rgs2(-/-) mice also display increased anxiety responses and decreased male aggression in the absence of cognitive or motor deficits. RGS2 also controls synaptic development and basal electrical activity in hippocampal CA1 neurons. Thus, RGS2 plays an important role in T cell activation, synapse development in the hippocampus, and emotive behaviors.

Aggression↗
PubMed2000

Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.

It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

Animals↗
PubMed2000

Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep.

The idea that sleep could serve a cognitive function has remained popular since Freud stated that dreams were "not nonsense" but a time to sort out experiences [S. Freud, Letter to Wilhelm Fliess, May 1897, in The Origins of Psychoanalysis - Personal Letters of Sigmund Freud, M. Bonaparte, A. Freud, E. Kris (Eds.), Translated by E. Mosbacher, J. Strachey, Basic Books and Imago Publishing, 1954]. Rapid eye movement (REM) sleep, which is associated with dream reports, is now known to be is important for acquisition of some tasks [A. Karni, D. Tanne, B.S. Rubenstein, J.J.M. Askenasy, D. Sagi, Dependence on REM sleep of overnight improvement of a perceptual skill, Science 265 (1994) 679-682; C. Smith, Sleep states and learning: a review of the animal literature, Biobehav. Rev. 9 (1985) 157-168]; although why this is so remains obscure. It has been proposed that memories may be consolidated during REM sleep or that forgetting of unnecessary material occurs in this state [F. Crick, G. Mitchison, The function of dream sleep, Nature 304 (1983) 111-114; D. Marr, Simple memory: a theory for archicortex, Philos. Trans. R. Soc. B. 262 (1971) 23-81]. We studied the firing of multiple single neurons in the hippocampus, a structure that is important for episodic memory, during familiar and novel experiences and in subsequent REM sleep. Cells active in familiar places during waking exhibited a reversal of firing phase relative to local theta oscillations in REM sleep. Because firing-phase can influence whether synapses are strengthened or weakened [C. Holscher, R. Anwyl, M.J. Rowan, Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo, J. Neurosci. 15 (1977) 6470-6477; P.T. Huerta, J.E. Lisman, Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro, Neuron 15 (1995) 1053-1063; C. Pavlides, Y.J. Greenstein, M. Grudman, J. Winson, Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm, Brain Res. 439 (1988) 383-387] this experience-dependent phase shift, which developed progressively over multiple sessions in the environment, is consistent with the hypothesis that circuits may be restructured during REM sleep by selectively strengthening recently acquired memories and weakening older ones.

Animals↗
PubMed2000

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors.

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer's disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer's disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.

Acetylcholinesterase↗
PubMed2000

Partial hippocampal inactivation: effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems.

Age Factors↗
PubMed2000

Age-related decrease in the Schaffer collateral-evoked EPSP in awake, freely behaving rats.

Synaptic response size in the CA1 region of the hippocampus in aged rats is reduced for a given stimulus intensity, compared with that elicited in young rats. Consistent with the in vitro findings of reduced Schaffer collateral-evoked CA1 EPSPs in old rats, the population currents evoked to iontophoretically applied AMPA are also smaller relative to the presynaptic fiber potential amplitude. On the other hand, the size of the presynaptic fiber potential and amplitude of unitary intra-cellularly recorded EPSP responses do not change across age in the CA1 region. These electrophysiological findings are consistent with the hypothesis that old rats have fewer functional synaptic contacts per Schaffer collateral axon than do young rats. The possibility that this age change arises as a result of a differential tissue recovery response to in vitro preparation was examined in the present study. CA1 presynaptic fiber potential and EPSP amplitudes evoked by the stimulation of Schaffer collateral afferents were studied in intact, freely behaving young and old rats. We confirmed in vivo the pattern of electrophysiophysiological results previously reported in vitro and found significant correlations between the synaptic response amplitudes and the accuracy of spatial behavior in the Morris swim task. The data suggest that changes in functional connectivity of old rats may be a significant contributor to cognitive changes during aging.

Afferent Pathways↗
PubMed2000

Determinants of clinical performance in a physical therapy program.

In admission decisions, allied health programs evaluate various factors that may include overall grade-point average (GPA), science GPA, GPA in the most recent 60 hours of course work, volunteer/work experience, and performance during an admission interview. Most use mathematical formulas based on these parameters, but the rationale for weighting each factor is not always clear. To determine whether pre-admission variables can differentiate between good and poor clinical performances, the authors compared pre-admission data from 118 graduates of a physical therapy (PT) baccalaureate program with their clinical performances. GPA in the PT curriculum was included to determine whether it was related to clinical performance, which was taken as the average of overall performance scores assigned to each student by his or her instructors at four clinical education sites. The students were divided into quartiles by clinical scores. One-way ANOVA was used to identify differences between quartiles for each variable (alpha level of p < 0.05). The interview score was the only pre-admission variable that differentiated between students who did and did not perform well in the clinic (p < 0.003). Those who performed better in the clinic also had higher PT GPAs (p < 0.0001). The interview format and scoring system used may easily be adapted for other programs. Recommendations are made regarding how to utilize interview scores in the admission decision.

Adult↗
PubMed1999

Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics.

During slow wave sleep (SWS), traces of neuronal activity patterns from preceding behavior can be observed in rat hippocampus and neocortex. The spontaneous reactivation of these patterns is manifested as the reinstatement of the distribution of pairwise firing-rate correlations within a population of simultaneously recorded neurons. The effects of behavioral state [quiet wakefulness, SWS, and rapid eye movement (REM)], interactions between two successive spatial experiences, and global modulation during 200 Hz electroencephalographic (EEG) "ripples" on pattern reinstatement were studied in CA1 pyramidal cell population recordings. Pairwise firing-rate correlations during often repeated experiences accounted for a significant proportion of the variance in these interactions in subsequent SWS or quiet wakefulness and, to a lesser degree, during SWS before the experience on a given day. The latter effect was absent for novel experiences, suggesting that a persistent memory trace develops with experience. Pattern reinstatement was strongest during sharp wave-ripple oscillations, suggesting that these events may reflect system convergence onto attractor states corresponding to previous experiences. When two different experiences occurred in succession, the statistically independent effects of both were evident in subsequent SWS. Thus, the patterns of neural activity reemerge spontaneously, and in an interleaved manner, and do not necessarily reflect persistence of an active memory (i.e., reverberation). Firing-rate correlations during REM sleep were not related to the preceding familiar experience, possibly as a consequence of trace decay during the intervening SWS. REM episodes also did not detectably influence the correlation structure in subsequent SWS, suggesting a lack of strengthening of memory traces during REM sleep, at least in the case of familiar experiences.

Animals↗
PubMed1999

Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles.

We used fluorescent in-situ hybridization and confocal microscopy to monitor the subcellular distribution of the immediate-early gene Arc. Arc RNA appeared in discrete intranuclear foci within minutes of neuronal activation and subsequently disappeared from the nucleus and accumulated in the cytoplasm by 30 minutes. The time course of nuclear versus cytoplasmic Arc RNA accumulation was distinct, and could therefore be used to infer the activity history of individual neurons at two times. Following sequential exposure of rats to two different environments or to the same environment twice, the proportion of CA1 neurons with cytoplasmic, nuclear or overlapping Arc expression profiles matched predictions derived from ensemble neurophysiological recordings of hippocampal neuronal ensembles. Arc gene induction is thus specifically linked to neural encoding processes.

Animals↗
PubMed1998

Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity.

Long-term neuronal plasticity is known to be dependent on rapid de novo synthesis of mRNA and protein, and recent studies provide insight into the molecules involved in this response. Here, we demonstrate that mRNA encoding a member of the regulator of G-protein signaling (RGS) family, RGS2, is rapidly induced in neurons of the hippocampus, cortex, and striatum in response to stimuli that evoke plasticity. Although several members of the RGS family are expressed in brain with discrete neuronal localizations, RGS2 appears unique in that its expression is dynamically responsive to neuronal activity. In biochemical assays, RGS2 stimulates the GTPase activity of the alpha subunit of Gq and Gi1. The effect on Gi1 was observed only after reconstitution of the protein in phospholipid vesicles containing M2 muscarinic acetylcholine receptors. RGS2 also inhibits both Gq- and Gi-dependent responses in transfected cells. These studies suggest a novel mechanism linking neuronal activity and signal transduction.

Animals↗
PubMed1998

Upf1 and Upf2 proteins mediate normal yeast mRNA degradation when translation initiation is limited.

mRNA degradation is coupled with the process of mRNA translation. For example, an mRNA molecule, on which translation is prematurely terminated because of a nonsense codon, may be rapidly degraded. This nonsense-mediated mRNA decay in the yeast Saccharomyces cerevisiae is mediated by the Upf1 and Upf2 proteins. Yeast mRNAs can also be selectively destabilized by limiting the rate of translation initiation. Two such destabilized mRNAs, from the SSA1 and SSA2 genes, have been identified using temperature-sensitive mutations affecting the Prt1 component of eukaryotic initiation factor 3. For SSA1 and SSA2 mRNAs, and for structurally modified SSA mRNA derivatives, I show here that degradation is triggered when translation initiation is limited but ongoing. This initiation-dependent mRNA degradation is limited to a subset of mRNAs that includes at least those from the SSA1 and SSA2 genes, and occurs through Upf1- and Upf2-mediated processes, although sequence elements characteristic of nonsense-mediated decay are not evident in these mRNAs.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Reactivation of neuronal ensembles in hippocampal dentate gyrus during sleep after spatial experience.

Patterns of neuronal activity recorded in CA1 of the hippocampus and in neocortex during waking-behavior, are reactivated during subsequent slow-wave sleep (SWS). It has been suggested that this reactivation may originate in the hippocampal CA3 region, where modifiable excitatory recurrent connections are abundant and where sharp-waves in which the reactivation is most robust, appear to arise. The present experiment investigated whether ensemble firing patterns of granule cells in the fascia dentata (FD), an area 'upstream' from CA3, are also reactivated during sleep. Populations of FD granule cells were recorded from during spatial behavior and during prior and subsequent SWS. firing rate correlations between cell-pairs with overlapping place fields were significantly enhanced during post behavioral sleep compared to pre behavioral sleep. Correlations between cells with non-overlapping place fields or which were silent during maze behavior, were not changed. Thus reactivation of experience-specific correlation states also occurs in granule cells during sleep. Because these cells do not have excitatory interconnections, but form a major input to CA3 pyramidal cells, current models predicted that sleep reactivation would appear first in CA3. There are, however, both extensive polysynaptic excitatory interactions among granule cells and feedback from CA3 pyramidal cells. Granule cells also receive indirect input from neocortical regions known to undergo trace reactivation. Although a simple model for a CA3 origin of the reactivation phenomenon cannot be confirmed, the present results extend our understanding of the generality of this phenomenon.

Animals↗
PubMed1997

Memory reprocessing in corticocortical and hippocampocortical neuronal ensembles.

Hippocampal cells that fire together during behaviour exhibit enhanced activity correlations during subsequent sleep, with some preservation of temporal order information. Thus, information reflecting experiences during behaviour is re-expressed in hippocampal circuits during subsequent 'offline' periods, as postulated by some theories of memory consolidation. If the hippocampus orchestrates the reinstatement of experience-specific activity patterns in the neocortex, as also postulated by such theories, then correlation patterns both within the neocortex and between hippocampus and neocortex should also re-emerge during sleep. Ensemble recordings were made in the posterior parietal neocortex, in CA1, and simultaneously in both areas, in seven rats. Each session involved an initial sleep episode (S1), behaviour on a simple maze (M), and subsequent sleep (S2). The ensemble activity-correlation structure within and between areas during S2 resembled that of M more closely than did the correlation pattern of S1. Temporal order (i.e. the asymmetry of the cross-correlogram) was also preserved within, but not between, structures. Thus, traces of recent experience are re-expressed in both hippocampal and neocortical circuits during sleep, and the representations in the two areas tend to correspond to the same experience. The poorer preservation of temporal firing biases between neurons in the different regions may reflect the less direct synaptic coupling between regions than within them. Alternatively, it could result from a shift, between behavioural states, in the relative dominance relations in the corticohippocampal dialogue. Between-structure order will be disrupted, for example, if, during behaviour, neocortical patterns tend to drive corresponding hippocampal patterns, whereas during sleep the reverse occurs. This possibility remains to be investigated.

Animals↗
PubMed1997

The effect of aging on experience-dependent plasticity of hippocampal place cells.

The firing characteristics of 1437 CA1 pyramidal neurons were studied in relation to both spatial location and the phase of the theta rhythm in healthy young and old rats performing a simple spatial task on a rectangular track. The old rats had previously been found to be deficient on the Morris spatial learning task. Age effects on the theta rhythm per se were minimal. Theta amplitude and frequency during rapid eye movement sleep were virtually identical. During behavior, theta frequency was slightly reduced with age. In both groups, cell firing occurred at progressively earlier phases of the theta rhythm as the rat traversed the place field of the cell (i. e., there was "phase precession," as reported by others). The net phase shift did not differ between age groups. The main finding of the study was a loss of experience-dependent plasticity in the place fields of old rats. During the first lap around the track on each day, the initial sizes of the place fields were the same between ages; however, place fields of young rats, but not old, expanded significantly during the first few laps around the track in a given recording session. As the place fields expanded, the rate of change of firing with phase slowed accordingly, so that the net phase change remained constant. Thus changes in field size and phase precession are coupled. A deficit in plasticity of place fields in old rats may lead to a less accurate population code for spatial location.

Action Potentials↗