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C A Barnes

Publications and source records attributed to C A Barnes.

151 records · Page 9Linked to original sources

Cortical representation of motion during unrestrained spatial navigation in the rat.

Neural activity related to unrestrained movement through space was studied in rat sensorimotor and posterior parietal cortices during performance of an eight-arm, radial maze task. Nearly half of the cells exhibited movement-related activity that discriminated among three basic modes of locomotion: left turns, right turns, and forward motion. Correlates ranged from strong excitation (relative to the still condition) to strong inhibition, and were distributed among the movement modes in a variety of different ways. For example, cells that discriminated between clockwise and counterclockwise turns did so with either antagonistic responses or simple excitation or inhibition. Others showed either excitation or inhibition relative to both turning and the still condition, and hence were selective for forward motion. Many cells exhibited somatosensory responsiveness; however, in agreement with findings of others, motion correlates could rarely be sensibly explained by the somatosensory response. Moreover, movement correlates sometimes varied considerably with spatial context. Some cells exhibited more complex motion correlates, such as an apparent dependence on the nature of the preceding movement. Irrespective of the specific sensory or motor determinants of cell activity, which varied considerably among cells, the posterior neocortex of the rat appears to generate a robust and redundant internal representation of body motion through space. Such a representation could be useful in constructing "cognitive maps" of the environment.

Animals↗

Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks.

Single cells were recorded with 'tetrodes' in regions of the rat medial prefrontal cortex, including those which are targets of hippocampal afferents, while rats were performing three different behavioral tasks: (i) an eight-arm radial maze, spatial working memory task, (ii) a figure-eight track, delayed spatial alternation task, and (iii) a random food search task in a square chamber. Among 187 recorded units, very few exhibited any evidence of place-specific firing on any of the behavioral tasks, except to the extent that different spatial locations were related to distinct phases of the task. Furthermore, no prefrontal unit showed unambiguous spatially dependent delay activity that might mediate working memory for spatial locations. Rather, the cells exhibited diverse correlates that were generally associated with the behavioral requirements of performing the task. This included firing related to intertrial intervals, onset or end of trials, selection of specific arms on the eight-arm radial maze, delay periods, approach to or departure from goals, and selection of paths on the figure-eight track. Although a small number of cells showed similar behavioral correlates across tasks, the majority of cells showed no consistent correlate when recorded across multiple tasks. Furthermore, some units did not exhibit altered firing patterns in any of the three tasks, while others showed changes in firing that were not consistently related to specific behaviors or task components. These results are in agreement with previous lesion and behavioral studies in rats that suggest a prefrontal cortical role in encoding 'rules' (i.e. structural features) or behavioral sequences within a task but not in encoding allocentric spatial information. Given that the hippocampal projection to this cortical region is capable of undergoing LTP, our data lead to the hypothesis that the role of this projection is not to impose spatial representations upon prefrontal activity, but to provide a mechanism for learning the spatial context in which particular behaviors are appropriate.

Action Potentials↗

Functional integrity of NMDA-dependent LTP induction mechanisms across the lifespan of F-344 rats.

Previous studies have reported a lack of an age effect in the induction of long-term potentiation (LTP) at CA1 synapses, using robust (supramaximal) stimulation parameters, but an apparent age effect on the induction threshold of LTP using less robust stimulation, in the perithreshold region. These findings have led to the suggestion that old animals may experience an alteration either in the efficacy of activation of N-methyl-D-aspartate (NMDA) receptors or in the metabolic processes subsequent to NMDA receptor activation that lead to LTP expression. An alternative explanation for the apparent threshold change in old animals is that, because of the known reduction of the intracellularly recorded, compound EPSP magnitude in old rats, equivalent electrical stimulation results in a smaller effective depolarization of the postsynaptic cells and a consequently less effective activation of NMDA receptors, which are otherwise functionally normal. To distinguish between these two hypotheses, weak orthodromic stimulation was paired with intracellularly applied current pulses, thus holding constant the degree of postsynaptic depolarization. No differences in LTP induction threshold or magnitude were observed in a large sample of rats from three age groups. It is concluded that the NMDA receptor mechanisms and associated biochemical processes leading to LTP induction are not altered in aged F-344 rats. The reduced compound EPSP in old animals was reconfirmed in the present study, and a significant correlation was found in old rats between the magnitude of the EPSP at a fixed stimulus level and their performance on a spatial memory task.

Animals↗

Effects of age on the generalization and incubation of memory in the F344 rat.

Freezing (immobility) in the presence of aversive stimuli is a species-specific behavior that is used as an operational measure of fear. Conditioning of this response to discrete sensory stimuli and environmental context cues has been used as a tool to study the neuropsychology of memory dynamics and their development over the lifespan. Three age groups of F344 rats (3, 9, and 27 month) received tone-foot shock pairing (or tone only) in a distinctive chamber on two consecutive days. Separate subgroups of rats from each age group were then tested, at retention intervals of 1, 20, 40, or 60 days, for context-mediated fear in the environment in which they were trained, for generalization of the fear response to a novel chamber, and for fear of the tone. Beginning at day 20, the 27-month-old rats exhibited less freezing behavior than did younger rats when tested in the conditioning context. This age difference was a result of freezing behavior becoming progressively stronger with time in the two younger age groups, a phenomenon that has been referred to as memory incubation. Incubation of the contextual fear response was not detected in the old rats. In a novel context, all age groups exhibited significantly more freezing than did control animals. There was also pronounced incubation of this generalized freezing response, and the extent of incubation declined significantly with age. In the novel context, the freezing response to the tone was robust in all age groups and increased over time, in constant proportion to the degree of freezing elicited by the novel context itself, prior to tone onset. The fact that old animals are known to be relatively selectively impaired in forms of memory that depend on a functional hippocampus suggests a possible explanation for the reduced incubation effects seen in old rats; however, whether the increased expression of fear over time is mediated by a hippocampal-dependent memory consolidation process or whether it reflects a generalized increase in the gain of the circuitry mediating the fear response itself, remains to be determined.

Acoustic Stimulation↗

Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268.

Programs of gene activation may underlie long-term adaptive cellular responses to extracellular ligands. We have used a differential cDNA cloning strategy to identify genes that are strongly induced by excitatory stimuli in the adult rat hippocampus. Here, we report the rat cDNA sequence of a zinc-finger transcription factor, Egr3/Pilot, and characterize its regulated mRNA expression in brain. Egr3 mRNA is rapidly and transiently induced in neurons of the hippocampus and cortex by electroconvulsive seizure. mRNA levels peak 2 hr after the seizure and remain elevated for as long as 8 hr. Egr3 mRNA is also rapidly induced in granule cells of the dentate gyrus by synaptic NMDA receptor activation elicited by patterned stimulation of the perforant pathway and by drugs that alter dopamine neurotransmission in the striatum. Basal levels of Egr3 mRNA in the cortex appear to be driven by natural synaptic activity because monocular deprivation rapidly decreases Egr3 mRNA in the deafferented visual cortex. Aspects of the protein structure, sequence-specific DNA binding, transcriptional activity, and regulation of Egr3 are highly similar to another zinc-finger transcription factor, Egr1/zif268. Moreover, we demonstrate colocalization of Egr3 and zif268 mRNAs in neurons of normal and stimulated cortex. Our studies suggest that interactions between these coregulated transcription factors may be important in defining long-term, neuroplastic responses.

Amino Acid Sequence↗

Neurological and behavioral investigations of memory failure in aging animals.

Aged organisms show a decline in their ability to learn and remember in certain situations. For example, it appears that both aged humans and aged rats exhibit spatial memory deficits. It is more difficult for older organisms to learn about and to navigate accurately within a familiar environment than it is for younger organisms. Because the brain structure that is critically involved in this type of behavior (the hippocampus) is relatively well understood in the rat, a correlation of spatial behavior with hippocampal physiology has been particularly useful in the delineation of some of the potential brain changes responsible for memory changes with age. Evidence for an age-related deficit in spatial memory is presented that emphasizes the importance of the contribution of the spatial component to the learning/memory changes seen with age in rats. The contribution of changes in hippocampal synaptic plasticity and in the information processing characteristics of single hippocampal cells of old rats is also discussed in terms of the potential influence on old animals' performance on spatial tasks.

Aging↗