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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.

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Behavioral task and hippocampal recording sitesa, Continuous spatial alternation task21,25,64,69. The task environment is a W-shaped maze with a center arm and two outer arms. Reward (∼0.3 mL of sweetened evaporated milk) is dispensed through 3-cm diameter wells (designated “A,” “B,” and “C” for reference in data plots), located at the end of each arm. Rats are rewarded for performing the trajectory sequence shown, in which the correct destination after visiting the center well is the less recently visited outer well. All subjects stopped locomoting upon reaching the reward wells to check for (by licking) and consume reward. Subjects also stopped intermittently elsewhere on the track (most frequently at maze junctions), particularly in earlier exposures to the task. b, c, Example hippocampal histological sections showing tetrode tracks and electrolytic lesions in CA1, CA2, CA3, and DG. Nissl-stained sections show neuronal cell bodies in dark blue, while sections stained with Neurotrace show neuronal cell bodies in light grey. Panel b shows example sections with sites overlapping with the CA2 cytoarchitectural locus24,29-31,37,53-56 (enclosed by dotted lines; characterized by dispersion of the hippocampal cell layer in the region between CA1 and CA3). Filled arrowheads indicate sites overlapping with CA2, while empty arrowheads indicate non-CA2 recording sites. The CA2 site assignment was deliberately inclusive to maximize detection of units at CA2 with novel physiological responses (N units, Fig. 1, Extended Data Fig. 3). Scale bars: 500 μm. d, Coronal hippocampal section stained with a neuronal cell body marker (light grey; NeuroTrace) and CA2 marker (yellow; RGS1437,48,70). Bottom, magnified view of a track left by a CA2 site tetrode. Scale bars: 500 μm. e, Survey of recording sites included in the study data set. Left, diagram of recording site locations in a representative hippocampal section. Shown are recording sites (circles) of seven subjects from which coronal hippocampal sections were taken (CA1: 41 sites, CA2: 9 sites, CA3: 30 sites, DG: 7 sites; two additional CA2 sites near the septal pole of hippocampus not shown). Dotted lines enclose the CA2 anatomical locus, with overlapping recording sites shown as filled circles. The majority of CA1 recordings were in CA1c, while the majority of CA3 recordings were in CA3b.
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Figure 1: Behavioral task and hippocampal recording sitesa, Continuous spatial alternation task21,25,64,69. The task environment is a W-shaped maze with a center arm and two outer arms. Reward (∼0.3 mL of sweetened evaporated milk) is dispensed through 3-cm diameter wells (designated “A,” “B,” and “C” for reference in data plots), located at the end of each arm. Rats are rewarded for performing the trajectory sequence shown, in which the correct destination after visiting the center well is the less recently visited outer well. All subjects stopped locomoting upon reaching the reward wells to check for (by licking) and consume reward. Subjects also stopped intermittently elsewhere on the track (most frequently at maze junctions), particularly in earlier exposures to the task. b, c, Example hippocampal histological sections showing tetrode tracks and electrolytic lesions in CA1, CA2, CA3, and DG. Nissl-stained sections show neuronal cell bodies in dark blue, while sections stained with Neurotrace show neuronal cell bodies in light grey. Panel b shows example sections with sites overlapping with the CA2 cytoarchitectural locus24,29-31,37,53-56 (enclosed by dotted lines; characterized by dispersion of the hippocampal cell layer in the region between CA1 and CA3). Filled arrowheads indicate sites overlapping with CA2, while empty arrowheads indicate non-CA2 recording sites. The CA2 site assignment was deliberately inclusive to maximize detection of units at CA2 with novel physiological responses (N units, Fig. 1, Extended Data Fig. 3). Scale bars: 500 μm. d, Coronal hippocampal section stained with a neuronal cell body marker (light grey; NeuroTrace) and CA2 marker (yellow; RGS1437,48,70). Bottom, magnified view of a track left by a CA2 site tetrode. Scale bars: 500 μm. e, Survey of recording sites included in the study data set. Left, diagram of recording site locations in a representative hippocampal section. Shown are recording sites (circles) of seven subjects from which coronal hippocampal sections were taken (CA1: 41 sites, CA2: 9 sites, CA3: 30 sites, DG: 7 sites; two additional CA2 sites near the septal pole of hippocampus not shown). Dotted lines enclose the CA2 anatomical locus, with overlapping recording sites shown as filled circles. The majority of CA1 recordings were in CA1c, while the majority of CA3 recordings were in CA3b.

Mentions: We recorded neural activity in hippocampal subregions CA1, CA2, CA3, and DG (Fig. 1a) in rats engaged in a hippocampus-dependent spatial memory task21,25, with interleaved rest sessions in an enclosed box. In the task, subjects were trained to alternate between each of three locations (reward wells) in a W-shaped maze (Extended Data Fig. 1a). In examining single neuron (unit) activity, we observed principal units (Fig. 1b) that fired at continuously high rates during immobility (Extended Data Fig. 2a). This basic observation led us to investigate hippocampal activity in this behavioral state.


A hippocampal network for spatial coding during immobility and sleep
Behavioral task and hippocampal recording sitesa, Continuous spatial alternation task21,25,64,69. The task environment is a W-shaped maze with a center arm and two outer arms. Reward (∼0.3 mL of sweetened evaporated milk) is dispensed through 3-cm diameter wells (designated “A,” “B,” and “C” for reference in data plots), located at the end of each arm. Rats are rewarded for performing the trajectory sequence shown, in which the correct destination after visiting the center well is the less recently visited outer well. All subjects stopped locomoting upon reaching the reward wells to check for (by licking) and consume reward. Subjects also stopped intermittently elsewhere on the track (most frequently at maze junctions), particularly in earlier exposures to the task. b, c, Example hippocampal histological sections showing tetrode tracks and electrolytic lesions in CA1, CA2, CA3, and DG. Nissl-stained sections show neuronal cell bodies in dark blue, while sections stained with Neurotrace show neuronal cell bodies in light grey. Panel b shows example sections with sites overlapping with the CA2 cytoarchitectural locus24,29-31,37,53-56 (enclosed by dotted lines; characterized by dispersion of the hippocampal cell layer in the region between CA1 and CA3). Filled arrowheads indicate sites overlapping with CA2, while empty arrowheads indicate non-CA2 recording sites. The CA2 site assignment was deliberately inclusive to maximize detection of units at CA2 with novel physiological responses (N units, Fig. 1, Extended Data Fig. 3). Scale bars: 500 μm. d, Coronal hippocampal section stained with a neuronal cell body marker (light grey; NeuroTrace) and CA2 marker (yellow; RGS1437,48,70). Bottom, magnified view of a track left by a CA2 site tetrode. Scale bars: 500 μm. e, Survey of recording sites included in the study data set. Left, diagram of recording site locations in a representative hippocampal section. Shown are recording sites (circles) of seven subjects from which coronal hippocampal sections were taken (CA1: 41 sites, CA2: 9 sites, CA3: 30 sites, DG: 7 sites; two additional CA2 sites near the septal pole of hippocampus not shown). Dotted lines enclose the CA2 anatomical locus, with overlapping recording sites shown as filled circles. The majority of CA1 recordings were in CA1c, while the majority of CA3 recordings were in CA3b.
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Related In: Results  -  Collection

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Figure 1: Behavioral task and hippocampal recording sitesa, Continuous spatial alternation task21,25,64,69. The task environment is a W-shaped maze with a center arm and two outer arms. Reward (∼0.3 mL of sweetened evaporated milk) is dispensed through 3-cm diameter wells (designated “A,” “B,” and “C” for reference in data plots), located at the end of each arm. Rats are rewarded for performing the trajectory sequence shown, in which the correct destination after visiting the center well is the less recently visited outer well. All subjects stopped locomoting upon reaching the reward wells to check for (by licking) and consume reward. Subjects also stopped intermittently elsewhere on the track (most frequently at maze junctions), particularly in earlier exposures to the task. b, c, Example hippocampal histological sections showing tetrode tracks and electrolytic lesions in CA1, CA2, CA3, and DG. Nissl-stained sections show neuronal cell bodies in dark blue, while sections stained with Neurotrace show neuronal cell bodies in light grey. Panel b shows example sections with sites overlapping with the CA2 cytoarchitectural locus24,29-31,37,53-56 (enclosed by dotted lines; characterized by dispersion of the hippocampal cell layer in the region between CA1 and CA3). Filled arrowheads indicate sites overlapping with CA2, while empty arrowheads indicate non-CA2 recording sites. The CA2 site assignment was deliberately inclusive to maximize detection of units at CA2 with novel physiological responses (N units, Fig. 1, Extended Data Fig. 3). Scale bars: 500 μm. d, Coronal hippocampal section stained with a neuronal cell body marker (light grey; NeuroTrace) and CA2 marker (yellow; RGS1437,48,70). Bottom, magnified view of a track left by a CA2 site tetrode. Scale bars: 500 μm. e, Survey of recording sites included in the study data set. Left, diagram of recording site locations in a representative hippocampal section. Shown are recording sites (circles) of seven subjects from which coronal hippocampal sections were taken (CA1: 41 sites, CA2: 9 sites, CA3: 30 sites, DG: 7 sites; two additional CA2 sites near the septal pole of hippocampus not shown). Dotted lines enclose the CA2 anatomical locus, with overlapping recording sites shown as filled circles. The majority of CA1 recordings were in CA1c, while the majority of CA3 recordings were in CA3b.
Mentions: We recorded neural activity in hippocampal subregions CA1, CA2, CA3, and DG (Fig. 1a) in rats engaged in a hippocampus-dependent spatial memory task21,25, with interleaved rest sessions in an enclosed box. In the task, subjects were trained to alternate between each of three locations (reward wells) in a W-shaped maze (Extended Data Fig. 1a). In examining single neuron (unit) activity, we observed principal units (Fig. 1b) that fired at continuously high rates during immobility (Extended Data Fig. 2a). This basic observation led us to investigate hippocampal activity in this behavioral state.

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