Long-term dynamics of CA1 hippocampal place codes

Abstract

Via Ca 2+ -imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, for each day the ensemble representation of this environment involved a unique subset of cells. Yet, cells within the ∼15-25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.CA1 place cells are considered crucial for spatial memory, but data is limited regarding whether their representations of space evolve over time scales of weeks or more 1 . Some theories suggest place cells should retain stable place fields for long-term retention of familiar environments 1 . Alternatively, dynamic aspects of place coding may facilitate distinct memory traces of different events occurring in the same environment 2 .Due to technical limitations, it has been only partially explored if CA1 representations of familiar environments are stable or evolve over time. Electrical recordings from many tens of cells are feasible 3 , but it is challenging to record from the same cells longer than a few days. Data on place fields' stability has largely been from small numbers of cells recorded over at most a week [4][5][6][7][8][9][10] . These studies have demonstrated cells with stable place fields, but the data have been too sparse to assess how coding evolves at the ensemble level.To study long-term coding dynamics, we combined (Fig. 1a): a viral vector (AAV2/5-CamKIIα-GCaMP3) to express the Ca 2+ -indicator GCaMP3 11 in pyramidal cells; a chronic mouse preparation for time-lapse imaging of CA1 over weeks 12 ; and a miniaturized (<2 g) microscope for Ca 2+ -imaging in hundreds of cells in freely behaving mice 13 . We thereby tracked somatic Ca 2+ dynamics of 515-1040 pyramidal cells in individual mice as they repeatedly visited a familiar track over 45 days.

New methods for understanding systems consolidation

“…There are many differences between these experiments (species, procedure, intervals between tests, background labeling) that could account for this difference. However, a recent study by Ziv et al (2013) used optical imaging to examine place cell reactivation in mice and found that 25% of neurons in CA1 (with active place fields) were reactivated in the same environment 5 d later. This number decreased slightly over time to 5% when sessions were separated by 30 d. In this study, the authors used calcium imaging and a miniaturized head-mounted microscope to monitor neural activity as mice traversed a linear track.…”

Memory Retrieval in Mice and Men

“…This approach offers a level of temporal resolution and action potential sensitivity that is intermediate between physiological recording and IEG expression, with the advantage that the neurons are precisely identified anatomically and can be stably imaged over long time periods. This approach was used to simultaneously record the activity of between 500 and 1000 CA1 hippocampal neurons over 45 days while the animals ran on a linear track in a constant spatial environment (Ziv et al 2013). As seen in previous electrophysiological studies, on any given day, the neurons showed clear spatial firing fields with 20% of neurons meeting the criteria for place cells.…”

Face-selective neurons maintain consistent visual responses across months

“…And indeed, both theoretical (4) and experimental results from motor cortex (5,6) demonstrate that a network composed of unstable units may nonetheless exhibit stable performance. Recent recordings from the mouse hippocampus showed that reliable location signaling is driven largely by neurons that gradually enter and leave the population of functionally active place cells over the course of several days (7). In that study, only 15% of longitudinally monitored neurons were found to retain the same place fields in two sessions that were separated by one month.…”