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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

Hippocampal spatial coding in desynchronized sleepDetection of sleep states using hippocampal LFP. Left, 10-minute trace of aggregate hippocampal LFP amplitude during sleep, with times classified as LIA (yellow), SIA (green), or REM (R) periods. SWR rate was estimated by counting SWRs in 1-s bins and smoothing with a Gaussian (σ = 2 s). Right, kernel density estimate (Gaussian kernel, σ = 0.1) of aggregate hippocampal LFP amplitude during non-REM sleep for the recording epoch from which the plotted trace was taken. Grey line: amplitude threshold used to distinguish SIA (below threshold) and LIA (above threshold) periods. b, Sleep firing in two example CA2 N units. Top traces: wide-band LFP (Wide, 0.5-400 Hz, scale bar: 2 mV) and ripple-band LFP (Ripple, 150-250 Hz, scale bar: 300 μV) traces from a simultaneous recording in CA1. SWR, LIA, and SIA periods are plotted as pink, yellow, and green zones, respectively. Grey-filled trace (y-axis: 0 to 10 cm/s): head speed. Subsequent analysis in d-f indicated that SIA firing was dependent on whether the location at which the animal slept was near the spatial firing field of the CA2 N unit. c, Mean firing rates during rest epochs (mean ± s.e.m.; # of units: CA1: 400, CA3: 220, CA2 P: 126 units, CA2 N: 76 units). CA2 N units fired more during SIA than LIA (p = 0.011, signed-rank) and at higher rates than other unit populations during SIA periods (green) and during awake immobility periods (grey) (Kruskal-Wallis ANOVA, Tukey's post hoc tests; p < 0.001 for SIA; p = 0.0051 for awake immobility). As in Fig. 2c, these comparisons indicate population-level engagement in sleep states, encompassing both higher and lower rate firing as a result of spatially specific firing in single units. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001. d, Example spatial firing maps of two pairs of simultaneously recorded CA2 N units in the rest environment. Data from waking periods plotted. Upper plots: positions visited (grey) and positions where the unit fired (black points). Total number of spikes is reported at upper right. Lower plots: occupancy-normalized firing maps. Peak spatial firing rate is reported at upper right. Scale bar: 20 cm. e, Three example CA2 N units coding for nesting position. Shown are occupancy-normalized firing maps from awake periods in a rest recording epoch. Indicated on each map is the nesting position (circle, 5 cm radius) of the subject for a sleep period detected in the same recording epoch. For a given sleep period, the unit was classified either as SIA ON (>2 Hz firing rate during SIA; black circle) or SIA OFF (<2 Hz; white circle). Reported at left are the mean awake firing rates within (Nest IN) and outside (Nest OUT) the encircled nesting region. In the third example, two distinct nesting positions corresponding to two distinct sleep periods were observed. f, Nesting position specificity index distribution in CA1, CA3, and CA2 N unit populations. The CA1 and CA2 N populations met dual criteria (see Supplementary Methods) for nesting position coding, while the CA3 unit population did not. Mean ± s.e.m.: CA1, SIA ON (n = 18 units): 0.18 ± 0.09, p = 0.043; CA1, SIA OFF (n = 92): -0.26 ± 0.04, p < 10-6; CA3, SIA ON (n = 19): 0.09 ± 0.09, p = 0.47; CA3, SIA OFF (n = 58): -0.04 ± 0.04, p = 0.50, signed-rank; CA2 N, SIA ON (n = 18): 0.18 ± 0.06, p = 0.020; CA2 N, SIA OFF (n = 57): -0.12 ± 0.04, p = 0.0087. All statistical tests were signed-rank. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001 or p ≪ 0.001; n.s., not significant at p < 0.05.
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Figure 15: Hippocampal spatial coding in desynchronized sleepDetection of sleep states using hippocampal LFP. Left, 10-minute trace of aggregate hippocampal LFP amplitude during sleep, with times classified as LIA (yellow), SIA (green), or REM (R) periods. SWR rate was estimated by counting SWRs in 1-s bins and smoothing with a Gaussian (σ = 2 s). Right, kernel density estimate (Gaussian kernel, σ = 0.1) of aggregate hippocampal LFP amplitude during non-REM sleep for the recording epoch from which the plotted trace was taken. Grey line: amplitude threshold used to distinguish SIA (below threshold) and LIA (above threshold) periods. b, Sleep firing in two example CA2 N units. Top traces: wide-band LFP (Wide, 0.5-400 Hz, scale bar: 2 mV) and ripple-band LFP (Ripple, 150-250 Hz, scale bar: 300 μV) traces from a simultaneous recording in CA1. SWR, LIA, and SIA periods are plotted as pink, yellow, and green zones, respectively. Grey-filled trace (y-axis: 0 to 10 cm/s): head speed. Subsequent analysis in d-f indicated that SIA firing was dependent on whether the location at which the animal slept was near the spatial firing field of the CA2 N unit. c, Mean firing rates during rest epochs (mean ± s.e.m.; # of units: CA1: 400, CA3: 220, CA2 P: 126 units, CA2 N: 76 units). CA2 N units fired more during SIA than LIA (p = 0.011, signed-rank) and at higher rates than other unit populations during SIA periods (green) and during awake immobility periods (grey) (Kruskal-Wallis ANOVA, Tukey's post hoc tests; p < 0.001 for SIA; p = 0.0051 for awake immobility). As in Fig. 2c, these comparisons indicate population-level engagement in sleep states, encompassing both higher and lower rate firing as a result of spatially specific firing in single units. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001. d, Example spatial firing maps of two pairs of simultaneously recorded CA2 N units in the rest environment. Data from waking periods plotted. Upper plots: positions visited (grey) and positions where the unit fired (black points). Total number of spikes is reported at upper right. Lower plots: occupancy-normalized firing maps. Peak spatial firing rate is reported at upper right. Scale bar: 20 cm. e, Three example CA2 N units coding for nesting position. Shown are occupancy-normalized firing maps from awake periods in a rest recording epoch. Indicated on each map is the nesting position (circle, 5 cm radius) of the subject for a sleep period detected in the same recording epoch. For a given sleep period, the unit was classified either as SIA ON (>2 Hz firing rate during SIA; black circle) or SIA OFF (<2 Hz; white circle). Reported at left are the mean awake firing rates within (Nest IN) and outside (Nest OUT) the encircled nesting region. In the third example, two distinct nesting positions corresponding to two distinct sleep periods were observed. f, Nesting position specificity index distribution in CA1, CA3, and CA2 N unit populations. The CA1 and CA2 N populations met dual criteria (see Supplementary Methods) for nesting position coding, while the CA3 unit population did not. Mean ± s.e.m.: CA1, SIA ON (n = 18 units): 0.18 ± 0.09, p = 0.043; CA1, SIA OFF (n = 92): -0.26 ± 0.04, p < 10-6; CA3, SIA ON (n = 19): 0.09 ± 0.09, p = 0.47; CA3, SIA OFF (n = 58): -0.04 ± 0.04, p = 0.50, signed-rank; CA2 N, SIA ON (n = 18): 0.18 ± 0.06, p = 0.020; CA2 N, SIA OFF (n = 57): -0.12 ± 0.04, p = 0.0087. All statistical tests were signed-rank. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001 or p ≪ 0.001; n.s., not significant at p < 0.05.

Mentions: To test this possibility, we evaluated hippocampal neural activity during rest sessions. First, during sleep, we observed periods of high-amplitude LFP, corresponding to a hippocampal sleep state dominated by SWRs (termed LIA1,18,34,35), frequently interrupted by periods of low-amplitude LFP in which the subject did not rouse, which we identified as periods of SIA (Fig. 5a). Next, in examining unit firing during sleep, we observed striking instances in which N units fired preferentially during SIA periods, falling silent during LIA (Fig. 5b). Analogously to awake immobility in the task (Fig. 2c), the N unit population fired at higher rates than all other unit populations during SIA (green, Fig. 5c) and also during awake immobility in the rest environment (dark grey, Fig. 5c). However, unlike the task condition, there was no significant overall correlation between firing rate and speed for N units during awake periods in the rest environment (Extended Data Fig. 10a), indicating that properties of the task maze or the cognitive demands of the task have essential roles in regulating N unit firing.


A hippocampal network for spatial coding during immobility and sleep
Hippocampal spatial coding in desynchronized sleepDetection of sleep states using hippocampal LFP. Left, 10-minute trace of aggregate hippocampal LFP amplitude during sleep, with times classified as LIA (yellow), SIA (green), or REM (R) periods. SWR rate was estimated by counting SWRs in 1-s bins and smoothing with a Gaussian (σ = 2 s). Right, kernel density estimate (Gaussian kernel, σ = 0.1) of aggregate hippocampal LFP amplitude during non-REM sleep for the recording epoch from which the plotted trace was taken. Grey line: amplitude threshold used to distinguish SIA (below threshold) and LIA (above threshold) periods. b, Sleep firing in two example CA2 N units. Top traces: wide-band LFP (Wide, 0.5-400 Hz, scale bar: 2 mV) and ripple-band LFP (Ripple, 150-250 Hz, scale bar: 300 μV) traces from a simultaneous recording in CA1. SWR, LIA, and SIA periods are plotted as pink, yellow, and green zones, respectively. Grey-filled trace (y-axis: 0 to 10 cm/s): head speed. Subsequent analysis in d-f indicated that SIA firing was dependent on whether the location at which the animal slept was near the spatial firing field of the CA2 N unit. c, Mean firing rates during rest epochs (mean ± s.e.m.; # of units: CA1: 400, CA3: 220, CA2 P: 126 units, CA2 N: 76 units). CA2 N units fired more during SIA than LIA (p = 0.011, signed-rank) and at higher rates than other unit populations during SIA periods (green) and during awake immobility periods (grey) (Kruskal-Wallis ANOVA, Tukey's post hoc tests; p < 0.001 for SIA; p = 0.0051 for awake immobility). As in Fig. 2c, these comparisons indicate population-level engagement in sleep states, encompassing both higher and lower rate firing as a result of spatially specific firing in single units. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001. d, Example spatial firing maps of two pairs of simultaneously recorded CA2 N units in the rest environment. Data from waking periods plotted. Upper plots: positions visited (grey) and positions where the unit fired (black points). Total number of spikes is reported at upper right. Lower plots: occupancy-normalized firing maps. Peak spatial firing rate is reported at upper right. Scale bar: 20 cm. e, Three example CA2 N units coding for nesting position. Shown are occupancy-normalized firing maps from awake periods in a rest recording epoch. Indicated on each map is the nesting position (circle, 5 cm radius) of the subject for a sleep period detected in the same recording epoch. For a given sleep period, the unit was classified either as SIA ON (>2 Hz firing rate during SIA; black circle) or SIA OFF (<2 Hz; white circle). Reported at left are the mean awake firing rates within (Nest IN) and outside (Nest OUT) the encircled nesting region. In the third example, two distinct nesting positions corresponding to two distinct sleep periods were observed. f, Nesting position specificity index distribution in CA1, CA3, and CA2 N unit populations. The CA1 and CA2 N populations met dual criteria (see Supplementary Methods) for nesting position coding, while the CA3 unit population did not. Mean ± s.e.m.: CA1, SIA ON (n = 18 units): 0.18 ± 0.09, p = 0.043; CA1, SIA OFF (n = 92): -0.26 ± 0.04, p < 10-6; CA3, SIA ON (n = 19): 0.09 ± 0.09, p = 0.47; CA3, SIA OFF (n = 58): -0.04 ± 0.04, p = 0.50, signed-rank; CA2 N, SIA ON (n = 18): 0.18 ± 0.06, p = 0.020; CA2 N, SIA OFF (n = 57): -0.12 ± 0.04, p = 0.0087. All statistical tests were signed-rank. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001 or p ≪ 0.001; n.s., not significant at p < 0.05.
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Figure 15: Hippocampal spatial coding in desynchronized sleepDetection of sleep states using hippocampal LFP. Left, 10-minute trace of aggregate hippocampal LFP amplitude during sleep, with times classified as LIA (yellow), SIA (green), or REM (R) periods. SWR rate was estimated by counting SWRs in 1-s bins and smoothing with a Gaussian (σ = 2 s). Right, kernel density estimate (Gaussian kernel, σ = 0.1) of aggregate hippocampal LFP amplitude during non-REM sleep for the recording epoch from which the plotted trace was taken. Grey line: amplitude threshold used to distinguish SIA (below threshold) and LIA (above threshold) periods. b, Sleep firing in two example CA2 N units. Top traces: wide-band LFP (Wide, 0.5-400 Hz, scale bar: 2 mV) and ripple-band LFP (Ripple, 150-250 Hz, scale bar: 300 μV) traces from a simultaneous recording in CA1. SWR, LIA, and SIA periods are plotted as pink, yellow, and green zones, respectively. Grey-filled trace (y-axis: 0 to 10 cm/s): head speed. Subsequent analysis in d-f indicated that SIA firing was dependent on whether the location at which the animal slept was near the spatial firing field of the CA2 N unit. c, Mean firing rates during rest epochs (mean ± s.e.m.; # of units: CA1: 400, CA3: 220, CA2 P: 126 units, CA2 N: 76 units). CA2 N units fired more during SIA than LIA (p = 0.011, signed-rank) and at higher rates than other unit populations during SIA periods (green) and during awake immobility periods (grey) (Kruskal-Wallis ANOVA, Tukey's post hoc tests; p < 0.001 for SIA; p = 0.0051 for awake immobility). As in Fig. 2c, these comparisons indicate population-level engagement in sleep states, encompassing both higher and lower rate firing as a result of spatially specific firing in single units. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001. d, Example spatial firing maps of two pairs of simultaneously recorded CA2 N units in the rest environment. Data from waking periods plotted. Upper plots: positions visited (grey) and positions where the unit fired (black points). Total number of spikes is reported at upper right. Lower plots: occupancy-normalized firing maps. Peak spatial firing rate is reported at upper right. Scale bar: 20 cm. e, Three example CA2 N units coding for nesting position. Shown are occupancy-normalized firing maps from awake periods in a rest recording epoch. Indicated on each map is the nesting position (circle, 5 cm radius) of the subject for a sleep period detected in the same recording epoch. For a given sleep period, the unit was classified either as SIA ON (>2 Hz firing rate during SIA; black circle) or SIA OFF (<2 Hz; white circle). Reported at left are the mean awake firing rates within (Nest IN) and outside (Nest OUT) the encircled nesting region. In the third example, two distinct nesting positions corresponding to two distinct sleep periods were observed. f, Nesting position specificity index distribution in CA1, CA3, and CA2 N unit populations. The CA1 and CA2 N populations met dual criteria (see Supplementary Methods) for nesting position coding, while the CA3 unit population did not. Mean ± s.e.m.: CA1, SIA ON (n = 18 units): 0.18 ± 0.09, p = 0.043; CA1, SIA OFF (n = 92): -0.26 ± 0.04, p < 10-6; CA3, SIA ON (n = 19): 0.09 ± 0.09, p = 0.47; CA3, SIA OFF (n = 58): -0.04 ± 0.04, p = 0.50, signed-rank; CA2 N, SIA ON (n = 18): 0.18 ± 0.06, p = 0.020; CA2 N, SIA OFF (n = 57): -0.12 ± 0.04, p = 0.0087. All statistical tests were signed-rank. Asterisks: *, p < 0.05; **, p < 0.01; ***, p < 0.001 or p ≪ 0.001; n.s., not significant at p < 0.05.
Mentions: To test this possibility, we evaluated hippocampal neural activity during rest sessions. First, during sleep, we observed periods of high-amplitude LFP, corresponding to a hippocampal sleep state dominated by SWRs (termed LIA1,18,34,35), frequently interrupted by periods of low-amplitude LFP in which the subject did not rouse, which we identified as periods of SIA (Fig. 5a). Next, in examining unit firing during sleep, we observed striking instances in which N units fired preferentially during SIA periods, falling silent during LIA (Fig. 5b). Analogously to awake immobility in the task (Fig. 2c), the N unit population fired at higher rates than all other unit populations during SIA (green, Fig. 5c) and also during awake immobility in the rest environment (dark grey, Fig. 5c). However, unlike the task condition, there was no significant overall correlation between firing rate and speed for N units during awake periods in the rest environment (Extended Data Fig. 10a), indicating that properties of the task maze or the cognitive demands of the task have essential roles in regulating N unit firing.

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