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A hippocampal network for spatial coding during immobility and sleep

View Article: PubMed Central - PubMed

ABSTRACT

How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has stood unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and furthermore does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signaling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.

No MeSH data available.


Related in: MedlinePlus

Firing properties of CA1, CA2, and CA3 unitsa, Peri-SWR time histograms (PSTHs; SWR onset at t = 0) of firing for all principal units in the task unit set. SWRs from both task and rest epochs were used to calculate PSTHs (1-ms bins), which were smoothed with a Gaussian kernel (σ = 10 ms). Each unit's mean PSTH was then z-scored (color bar) and plotted in a row. Units are sorted by the time of the maximum z-scored rate from 0 to +100 ms. b, PSTHs for the four hippocampal unit populations (mean ± s.e.m.; # of units: CA1: 478 units; CA3: 271; CA2 P: 142; CA2 N: 84) analyzed in this study. Using formal criteria (described in Supplementary Methods), units that were inhibited during SWRs constituted a majority subset (56 of 84) of N units, and were observed in every subject with CA2 site recordings (5 subjects, inhibition apparent in examples in Fig. 1d and N unit PSTHs in a). Here, the reduction of firing in these neurons manifests in the N unit population response as a dip in firing rate at the time of SWRs (N unit population in blue), in contrast to the CA1, CA3, and CA2 P unit populations, all of which showed sharp increases in firing during SWRs19. Time bins: 5 ms. c, Proportion of N units in CA2 site recordings. Upper plots: spike amplitudes measured on two channels of a tetrode for two example CA2 site recordings (left and right). Colors indicate spikes of N (blue-based tones) and P (red-based tones) units. The number of well-isolated principal units of each type is reported at upper right. Scale bars (x and y): 100 μV. Lower plot: proportion of N units across CA2 site recordings with at least four clustered putative principal units. CA2 recording sites typically reported N and P units concurrently, indicating that the spiking of two distinct hippocampal principal cell types was detectable at a single CA2 recording site. d, Unit spike counts in 15-minute task epochs for each principal unit population. The counts were taken from each unit's highest mean rate task epoch. Spikes that occurred during SWR periods were not included in these counts. e, Mean firing rate for each principal unit population (mean ± s.e.m). The mean rates were calculated from the highest rate epoch for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data): CA1: 454 units; CA2 P: 142; CA2 N: 84; CA3: 252. All spikes and epoch times were included. f, Peak firing rate for each principal unit population (mean ± s.e.m). The peak rates were estimated from the highest rate epochs for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. The peak rate was the maximum instantaneous firing rate (IFR) exhibited by the unit. Here, the IFR was estimated by convolving each unit's spike train (1-ms bins) with Gaussian kernels of different sizes (x-axis, times refer to s.d. of the kernel). TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data and at least 100 spikes in a rest epoch): CA1: 421, CA2 P: 138, CA2 N: 82, CA3: 197 units. All spikes and epoch times were included. g, Burst firing in each principal unit population. The burst index of a unit was defined as the proportion of inter-spike intervals (ISI) less than 6 ms73,74. Burst indices were calculated separately for three conditions: locomotion (left panels) and immobility (center) in task epochs, and also for rest epochs (right). In a given condition, a minimum of 100 spikes was required for a unit to be analyzed. Moreover, for locomotor and immobility periods from task epochs, only ISIs of spikes that were successive within single uninterrupted periods of a given type were included. Lastly, in this analysis, SWR periods were not excluded. Notably, CA2 N units showed high levels of bursting, suggesting that these units correspond to hippocampal principal (pyramidal) neurons58,59,61,75-78.
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Figure 3: Firing properties of CA1, CA2, and CA3 unitsa, Peri-SWR time histograms (PSTHs; SWR onset at t = 0) of firing for all principal units in the task unit set. SWRs from both task and rest epochs were used to calculate PSTHs (1-ms bins), which were smoothed with a Gaussian kernel (σ = 10 ms). Each unit's mean PSTH was then z-scored (color bar) and plotted in a row. Units are sorted by the time of the maximum z-scored rate from 0 to +100 ms. b, PSTHs for the four hippocampal unit populations (mean ± s.e.m.; # of units: CA1: 478 units; CA3: 271; CA2 P: 142; CA2 N: 84) analyzed in this study. Using formal criteria (described in Supplementary Methods), units that were inhibited during SWRs constituted a majority subset (56 of 84) of N units, and were observed in every subject with CA2 site recordings (5 subjects, inhibition apparent in examples in Fig. 1d and N unit PSTHs in a). Here, the reduction of firing in these neurons manifests in the N unit population response as a dip in firing rate at the time of SWRs (N unit population in blue), in contrast to the CA1, CA3, and CA2 P unit populations, all of which showed sharp increases in firing during SWRs19. Time bins: 5 ms. c, Proportion of N units in CA2 site recordings. Upper plots: spike amplitudes measured on two channels of a tetrode for two example CA2 site recordings (left and right). Colors indicate spikes of N (blue-based tones) and P (red-based tones) units. The number of well-isolated principal units of each type is reported at upper right. Scale bars (x and y): 100 μV. Lower plot: proportion of N units across CA2 site recordings with at least four clustered putative principal units. CA2 recording sites typically reported N and P units concurrently, indicating that the spiking of two distinct hippocampal principal cell types was detectable at a single CA2 recording site. d, Unit spike counts in 15-minute task epochs for each principal unit population. The counts were taken from each unit's highest mean rate task epoch. Spikes that occurred during SWR periods were not included in these counts. e, Mean firing rate for each principal unit population (mean ± s.e.m). The mean rates were calculated from the highest rate epoch for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data): CA1: 454 units; CA2 P: 142; CA2 N: 84; CA3: 252. All spikes and epoch times were included. f, Peak firing rate for each principal unit population (mean ± s.e.m). The peak rates were estimated from the highest rate epochs for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. The peak rate was the maximum instantaneous firing rate (IFR) exhibited by the unit. Here, the IFR was estimated by convolving each unit's spike train (1-ms bins) with Gaussian kernels of different sizes (x-axis, times refer to s.d. of the kernel). TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data and at least 100 spikes in a rest epoch): CA1: 421, CA2 P: 138, CA2 N: 82, CA3: 197 units. All spikes and epoch times were included. g, Burst firing in each principal unit population. The burst index of a unit was defined as the proportion of inter-spike intervals (ISI) less than 6 ms73,74. Burst indices were calculated separately for three conditions: locomotion (left panels) and immobility (center) in task epochs, and also for rest epochs (right). In a given condition, a minimum of 100 spikes was required for a unit to be analyzed. Moreover, for locomotor and immobility periods from task epochs, only ISIs of spikes that were successive within single uninterrupted periods of a given type were included. Lastly, in this analysis, SWR periods were not excluded. Notably, CA2 N units showed high levels of bursting, suggesting that these units correspond to hippocampal principal (pyramidal) neurons58,59,61,75-78.

Mentions: We first found that, although SWRs were prominent during immobility, SWR periods comprised only a small proportion of time spent immobile (<10%, Extended Data Fig. 2b), suggesting that SWRs could not account for the observed continuous firing. Next, in examining unit firing at the time of SWRs, we were struck by putative principal units recorded in CA2 that consistently decreased firing during both task and rest SWRs, in contrast to CA1 and CA3 principal units, which increased firing (Fig. 1c, d). Indeed virtually all CA1 and CA3 principal units fired more during SWRs (permutation tests at p < 0.05, CA1: 478 out of 489 units, CA3: 271 out of 276 units), while a substantial proportion of putative principal units recorded at CA2 sites were either inhibited or showed no change in firing rate during SWRs, despite otherwise firing hundreds to thousands of spikes during single task epochs (84 out of 226 CA2 site units, with 56 of 84 significantly inhibited during SWRs; Fig. 1e, Extended Data Fig. 3). We termed these atypical units at CA2 sites “N” units (non-positively modulated by SWRs) to distinguish them from conventionally responding “P” units (positively modulated).


A hippocampal network for spatial coding during immobility and sleep
Firing properties of CA1, CA2, and CA3 unitsa, Peri-SWR time histograms (PSTHs; SWR onset at t = 0) of firing for all principal units in the task unit set. SWRs from both task and rest epochs were used to calculate PSTHs (1-ms bins), which were smoothed with a Gaussian kernel (σ = 10 ms). Each unit's mean PSTH was then z-scored (color bar) and plotted in a row. Units are sorted by the time of the maximum z-scored rate from 0 to +100 ms. b, PSTHs for the four hippocampal unit populations (mean ± s.e.m.; # of units: CA1: 478 units; CA3: 271; CA2 P: 142; CA2 N: 84) analyzed in this study. Using formal criteria (described in Supplementary Methods), units that were inhibited during SWRs constituted a majority subset (56 of 84) of N units, and were observed in every subject with CA2 site recordings (5 subjects, inhibition apparent in examples in Fig. 1d and N unit PSTHs in a). Here, the reduction of firing in these neurons manifests in the N unit population response as a dip in firing rate at the time of SWRs (N unit population in blue), in contrast to the CA1, CA3, and CA2 P unit populations, all of which showed sharp increases in firing during SWRs19. Time bins: 5 ms. c, Proportion of N units in CA2 site recordings. Upper plots: spike amplitudes measured on two channels of a tetrode for two example CA2 site recordings (left and right). Colors indicate spikes of N (blue-based tones) and P (red-based tones) units. The number of well-isolated principal units of each type is reported at upper right. Scale bars (x and y): 100 μV. Lower plot: proportion of N units across CA2 site recordings with at least four clustered putative principal units. CA2 recording sites typically reported N and P units concurrently, indicating that the spiking of two distinct hippocampal principal cell types was detectable at a single CA2 recording site. d, Unit spike counts in 15-minute task epochs for each principal unit population. The counts were taken from each unit's highest mean rate task epoch. Spikes that occurred during SWR periods were not included in these counts. e, Mean firing rate for each principal unit population (mean ± s.e.m). The mean rates were calculated from the highest rate epoch for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data): CA1: 454 units; CA2 P: 142; CA2 N: 84; CA3: 252. All spikes and epoch times were included. f, Peak firing rate for each principal unit population (mean ± s.e.m). The peak rates were estimated from the highest rate epochs for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. The peak rate was the maximum instantaneous firing rate (IFR) exhibited by the unit. Here, the IFR was estimated by convolving each unit's spike train (1-ms bins) with Gaussian kernels of different sizes (x-axis, times refer to s.d. of the kernel). TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data and at least 100 spikes in a rest epoch): CA1: 421, CA2 P: 138, CA2 N: 82, CA3: 197 units. All spikes and epoch times were included. g, Burst firing in each principal unit population. The burst index of a unit was defined as the proportion of inter-spike intervals (ISI) less than 6 ms73,74. Burst indices were calculated separately for three conditions: locomotion (left panels) and immobility (center) in task epochs, and also for rest epochs (right). In a given condition, a minimum of 100 spikes was required for a unit to be analyzed. Moreover, for locomotor and immobility periods from task epochs, only ISIs of spikes that were successive within single uninterrupted periods of a given type were included. Lastly, in this analysis, SWR periods were not excluded. Notably, CA2 N units showed high levels of bursting, suggesting that these units correspond to hippocampal principal (pyramidal) neurons58,59,61,75-78.
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Figure 3: Firing properties of CA1, CA2, and CA3 unitsa, Peri-SWR time histograms (PSTHs; SWR onset at t = 0) of firing for all principal units in the task unit set. SWRs from both task and rest epochs were used to calculate PSTHs (1-ms bins), which were smoothed with a Gaussian kernel (σ = 10 ms). Each unit's mean PSTH was then z-scored (color bar) and plotted in a row. Units are sorted by the time of the maximum z-scored rate from 0 to +100 ms. b, PSTHs for the four hippocampal unit populations (mean ± s.e.m.; # of units: CA1: 478 units; CA3: 271; CA2 P: 142; CA2 N: 84) analyzed in this study. Using formal criteria (described in Supplementary Methods), units that were inhibited during SWRs constituted a majority subset (56 of 84) of N units, and were observed in every subject with CA2 site recordings (5 subjects, inhibition apparent in examples in Fig. 1d and N unit PSTHs in a). Here, the reduction of firing in these neurons manifests in the N unit population response as a dip in firing rate at the time of SWRs (N unit population in blue), in contrast to the CA1, CA3, and CA2 P unit populations, all of which showed sharp increases in firing during SWRs19. Time bins: 5 ms. c, Proportion of N units in CA2 site recordings. Upper plots: spike amplitudes measured on two channels of a tetrode for two example CA2 site recordings (left and right). Colors indicate spikes of N (blue-based tones) and P (red-based tones) units. The number of well-isolated principal units of each type is reported at upper right. Scale bars (x and y): 100 μV. Lower plot: proportion of N units across CA2 site recordings with at least four clustered putative principal units. CA2 recording sites typically reported N and P units concurrently, indicating that the spiking of two distinct hippocampal principal cell types was detectable at a single CA2 recording site. d, Unit spike counts in 15-minute task epochs for each principal unit population. The counts were taken from each unit's highest mean rate task epoch. Spikes that occurred during SWR periods were not included in these counts. e, Mean firing rate for each principal unit population (mean ± s.e.m). The mean rates were calculated from the highest rate epoch for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data): CA1: 454 units; CA2 P: 142; CA2 N: 84; CA3: 252. All spikes and epoch times were included. f, Peak firing rate for each principal unit population (mean ± s.e.m). The peak rates were estimated from the highest rate epochs for each unit, either among task (top, TASK) or rest (bottom, REST) epochs. The peak rate was the maximum instantaneous firing rate (IFR) exhibited by the unit. Here, the IFR was estimated by convolving each unit's spike train (1-ms bins) with Gaussian kernels of different sizes (x-axis, times refer to s.d. of the kernel). TASK # units (task unit set): CA1: 478 units; CA2 P: 142; CA2 N: 84; CA3: 271. REST # units (subset of task unit set with available rest epoch data and at least 100 spikes in a rest epoch): CA1: 421, CA2 P: 138, CA2 N: 82, CA3: 197 units. All spikes and epoch times were included. g, Burst firing in each principal unit population. The burst index of a unit was defined as the proportion of inter-spike intervals (ISI) less than 6 ms73,74. Burst indices were calculated separately for three conditions: locomotion (left panels) and immobility (center) in task epochs, and also for rest epochs (right). In a given condition, a minimum of 100 spikes was required for a unit to be analyzed. Moreover, for locomotor and immobility periods from task epochs, only ISIs of spikes that were successive within single uninterrupted periods of a given type were included. Lastly, in this analysis, SWR periods were not excluded. Notably, CA2 N units showed high levels of bursting, suggesting that these units correspond to hippocampal principal (pyramidal) neurons58,59,61,75-78.
Mentions: We first found that, although SWRs were prominent during immobility, SWR periods comprised only a small proportion of time spent immobile (<10%, Extended Data Fig. 2b), suggesting that SWRs could not account for the observed continuous firing. Next, in examining unit firing at the time of SWRs, we were struck by putative principal units recorded in CA2 that consistently decreased firing during both task and rest SWRs, in contrast to CA1 and CA3 principal units, which increased firing (Fig. 1c, d). Indeed virtually all CA1 and CA3 principal units fired more during SWRs (permutation tests at p < 0.05, CA1: 478 out of 489 units, CA3: 271 out of 276 units), while a substantial proportion of putative principal units recorded at CA2 sites were either inhibited or showed no change in firing rate during SWRs, despite otherwise firing hundreds to thousands of spikes during single task epochs (84 out of 226 CA2 site units, with 56 of 84 significantly inhibited during SWRs; Fig. 1e, Extended Data Fig. 3). We termed these atypical units at CA2 sites “N” units (non-positively modulated by SWRs) to distinguish them from conventionally responding “P” units (positively modulated).

View Article: PubMed Central - PubMed

ABSTRACT

How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has stood unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and furthermore does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signaling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.

No MeSH data available.


Related in: MedlinePlus