Search for: All records

Abstract Immediate‐early genes (IEGs) exhibit a rapid, transient transcription response to neuronal activation. Fluorescently labeled mRNA transcripts appear as bright intranuclear transcription foci (INF), which have been used as an all‐or‐nothing indicator of recent neuronal activity; however, it would be useful to know whether INF fluorescence can be used effectively to assess relative activations within a neural population. We quantified theHomer1a(H1a) response of hippocampal neurons to systematically varied numbers of exposures to the same places by inducing male Long‐Evans rats to run laps around a track. Previous studies reveal relatively stable firing rates across laps on a familiar track. A strong linear trend (r² > 0.9) in INF intensity was observed between 1 and 25 laps, after which INF intensity declined as a consequence of dispersion related to the greater elapsed time. When the integrated fluorescence of the entire nucleus was considered instead, the linear relationship extended to 50 laps. However, there was only an approximate doubling ofH1adetected for this 50‐fold variation in total spiking. Thus, the intranuclearH1aRNA fluorescent signal does provide a relative measure of how many times a set of neurons was activated over a ~10 min period, but the dynamic range and hence signal‐to‐noise ratios are poor. This low dynamic range may reflect previously reported reductions in the IEG response during repeated episodes of behavior over longer time scales. It remains to be determined how well theH1asignal reflects relative firing rates within a population of neurons in response to a single, discrete behavioral event. 

In early Alzheimer’s disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks. 

Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal–entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.