Differences in Hippocampal Neuronal Population Responses to Modifications of an Environmental Context: Evidence for Distinct, Yet Complementary, Functions of CA3 and CA1 Ensembles

Abstract

Understanding how the hippocampus processes information critical for establishing spatial and declarative memories will benefit greatly from determining not only what kind of information the hippocampus registers, but also how this information is processed across the different hippocampal subfields. We addressed this question using a novel immediate-early gene-based brain-imaging method (Arc/H1a catFISH) that allows comparisons of neuronal ensembles activated by two experiences separated by ϳ30 min. Rats exposed to the same environment twice activated CA3 and CA1 ensembles with a similarly high degree of overlap. Changing the identity or configuration of local cues, or changing distal cues, activated CA3 and CA1 ensembles with reduced overlap. Yet, the overlap was greater in CA3 than in CA1. In contrast, rats exposed to two completely different environments activated CA3 and CA1 ensembles with low overlap, and this overlap was even lower in CA3 compared with CA1. Thus, CA3 has a discontinuous, whereas CA1 has a graded, population response to alterations of an environment. Additionally, as indicated by the percentage of active neurons, the context representation was more sparse in CA3 (ϳ18%) than in CA1 (ϳ35%). Finally, CA3 and CA1 activity levels were not correlated within a session, arguing against a simple coactivation of these regions. Instead, the within-rat ratio of CA3/CA1 cell activity was correlated across sessions, suggesting that the balance of CA3/CA1 activity is individual specific. Taken together, these findings suggest that CA3 and CA1 neuronal ensembles perform distinct, yet complementary, functions in the processing of spatial and contextual information.

Cortical pattern separation and item-specific memory encoding

“…In bilateral lateral PFC, and right parietal regions, responses to parametrically varied conceptual and perceptual input similarity provided further evidence for pattern separation. The data are in line with computational predictions (Treves and Rolls, 1992;Vazdarjanova and Guzowski, 2004) and with findings of pattern separation and completion computations in sensory cortex in rodents (Aimone et al, 2011;Barnes et al, 2008). Bilateral prefrontal and left occipital cortex regions showing pattern separation activity were also engaged during encoding predicting subsequent true recognition, consistent with suggestions that cortical pattern separation contributes to successful itemspecific encoding.…”

“…Within the hippocampus, computational, electrophysiological and lesion evidence has implicated the dentate gyrus (DG) in pattern separation, and subfields CA3 and CA1 in pattern separation or completion, depending on the degree of overlap between incoming and existing representations (Gilbert et al, 2001;Guzowski et al, 2004;Leutgeb et al, 2007;Rolls, 2007;Vazdarjanova and Guzowski, 2004). High-resolution functional magnetic resonance imaging (fMRI) evidence from humans is consistent with these findings.…”

“…In contrast, pattern completion increases the representational overlap at output relative to input representations (O'Reilly and McClelland, 1994), approximated by a power function with increasing slope, i.e., very slight differences in activity occur between repeated and similar items, with only highly dissimilar items processed as if novel ( Fig. 1; Vazdarjanova and Guzowski, 2004). In regions showing repetition enhancement, the functions are the same but their direction is inverted (Fig.…”

“…Although the fMRA findings are suggestive of cortical pattern separation and completion, these processes are computationally defined in terms of their responses to parametrically varied input similarity (e.g., Treves and Rolls, 1992;Vazdarjanova and Guzowski, 2004). Therefore, examination of neural responses to graded change in input, i.e., to stimuli of varying similarity relative to previously presented items, can provide further support for their presence (Hunsaker and Kesner, 2013;Kumaran and Maguire, 2009).…”

Multiple repetitions reveal functionally and anatomically distinct patterns of hippocampal activity during continuous recognition memory

“…It is tempting, however, to relate these results to recent evidence indicating that the CA3 field exhibits more abrupt activity changes in response to changes in stimulus input than does CA1 -a distinction that is believed to correspond to the theoretical constructs of pattern separation versus completion, respectively (Bakker et al, 2008;Leutgeb et al, 2004;Vazdarjanova & Guzowski, 2004). From this perspective, the present findings reflect the tendency of CA3 to categorize input (in this case, new versus old items) in an 'all or none' fashion, while CA1 demonstrates a more continuous (less differentiated) response to the same change in input (Bakker et al, 2008).…”