scholarly journals Binding experience-relevant neuronal assemblies through disinhibition

2020 ◽  
Author(s):  
Raquel Garcia-Hernandez ◽  
José María Caramés ◽  
Elena Pérez-Montoyo ◽  
Santiago Canals
Keyword(s):  
Dentate Gyrus ◽  
Spatial Information ◽  
Granule Cells ◽  
Moderate Increase ◽  
The Novel ◽  
Memory Encoding ◽  
Neuronal Assemblies ◽  
Inhibitory Tone ◽  
Cell Inhibition ◽  
Perisomatic Inhibition

Granule cells in the dentate gyrus (DGgc), a brain region important for spatial learning, are part of the engrams formed when an animal explores a new context. Previous work showed that modulation of DGgc activity by perisomatic inhibition bidirectionally regulates memory encoding. Whether this result is due to a differential recruitment of experience-relevant neuronal assemblies or the functional connectivity between them, is not yet known. We combined pharmacogenetic tools (DREADDs) to increase or decrease the activity of parvalbumin (PV)-interneurons in DG while mice encoded spatial information in the Novel Object Location task (NOL). Sixty min after memory encoding in the NOL task animals were sacrificed and their brains processed and quantified for c-Fos staining. Exploration in the NOL task induced a robust increase in the number of c-Fos+ cells across hippocampal subfields. However, the number of c-Fos+ cells, both in the hippocampus and extra-hippocampal structures like the medial prefrontal cortex (mPFC) and the nucleus accumbens, was constant regardless of the inhibitory tone in the DG. Only a moderate increase in c-Fos intensity per cell in DGgc was found in the PV-cell inhibition group. In contrast, we found a significant increase in the correlation between the number of c-Fos+ cells in all quantified neuronal assemblies during PV-inhibition, and a decrease during activation. Together, these data reveal a critical regulatory role of perisomatic inhibition in the dentate gyrus in binding experience-relevant neuronal assemblies in memory.

scholarly journals Dentate gyrus somatostatin cells are required for contextual discrimination during episodic memory encoding

2019 ◽  
Author(s):  
Cristian Morales ◽  
Juan Facundo Morici ◽  
Nelson Espinosa ◽  
Agostina Sacson ◽  
Ariel Lara-Vasquez ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Molecular Layer ◽  
Memory Systems ◽  
Pattern Separation ◽  
Activity Levels ◽  
Memory Encoding ◽  
Somatostatin Cells ◽  
Somatostatin Neurons

AbstractEpisodic memory establishes and stores relations among the different elements of an experience, which are often similar and difficult to distinguish. Pattern separation, implemented by the dentate gyrus, is a neural mechanism that allows the discrimination of similar experiences by orthogonalizing synaptic inputs. Granule cells support such disambiguation by sparse rate coding, a process tightly controlled by highly diversified GABAergic neuronal populations, such as somatostatin-expressing cells which directly target the dendritic arbor of granule cells, massively innervated by entorhinal inputs reaching the molecular layer and conveying contextual information. Here, we tested the hypothesis that somatostatin neurons regulate the excitability of the dentate gyrus, thus controlling the efficacy of pattern separation during memory encoding in mice. Indeed, optogenetic suppression of dentate gyrus somatostatin neurons increased spiking activity in putative excitatory neurons and triggered dentate spikes. Moreover, optical inhibition of somatostatin neurons impaired both contextual and spatial discrimination of overlapping episodic-like memories during task acquisition. Importantly, effects were specific for similar environments, suggesting that pattern separation was selectively engaged when overlapping conditions ought to be distinguished. Overall, our results suggest that somatostatin cells regulate excitability in the dentate gyrus and are required for effective pattern separation during episodic memory encoding.Significance statementMemory systems must be able to discriminate stored representations of similar experiences in order to efficiently guide future decisions. This is solved by pattern separation, implemented in the dentate gyrus by granule cells to support episodic memory formation. The tonic inhibitory bombardment produced by multiple GABAergic cell populations maintains low activity levels in granule cells, permitting the process of pattern separation. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the dentate gyrus. Hence, somatostatin cells constitute an ideal candidate to regulate pattern separation. Here, by using optogenetic stimulation in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.

scholarly journals Parallel processing of sensory cue and spatial information in the Dentate Gyrus

2020 ◽  
Author(s):  
Sebnem Tuncdemir ◽  
Andres Grosmark ◽  
Gergely Turi ◽  
Amei Shank ◽  
John Bowler ◽  
...  
Keyword(s):  
Parallel Processing ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Spatial Information ◽  
Granule Cells ◽  
Spatial Location ◽  
Place Cells ◽  
On Line ◽  
Sensory Cue ◽  
Self Motion

Abstract During exploration, animals form an internal map of an environment by combining information about specific sensory cues or landmarks with the animal’s motion through space, a process which critically depends on the mammalian hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal trisynaptic circuit where self-motion and sensory cue information are integrated, yet it remains unknown how neurons within the DG encode both cue related (“what”) and spatial (“where”) information during cognitive map formation. Using two photon calcium imaging in head fixed mice running on a treadmill, along with on-line sensory cue manipulation at specific track locations, we have identified robust sensory cue responses in DG granule cells largely independent of spatial location. Granule cell cue responses are stable for long periods of time, selective for the modality of the stimulus and accompanied by strong inhibition of the firing of other active neurons. At the same time, there is a smaller fraction of neurons whose firing is spatially tuned but insensitive to the presentation of nearby cues, similar to traditional place cells. These results demonstrate the existence of “cue cells” in addition to the better characterized “place cells” in the DG, an important heterogeneity that has been previously overlooked. We hypothesize that the observed diversity of representations within the granule cell population may support parallel processing of complementary sensory and spatial information and impact the role of the dentate gyrus in spatial navigation and episodic memory.

scholarly journals Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Soyoun Kim ◽  
Dajung Jung ◽  
Sébastien Royer
Keyword(s):  
Dentate Gyrus ◽  
Spatial Information ◽  
Granule Cells ◽  
Place Cells ◽  
Competitive Learning ◽  
Spatial Representations ◽  
Mossy Cells ◽  
Object Locations ◽  
Treadmill Belt ◽  
The Continuum

Abstract Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.

GABA Uptake and Heterotransport Are Impaired in the Dentate Gyrus of Epileptic Rats and Humans With Temporal Lobe Sclerosis

2001 ◽  
Vol 85 (4) ◽  
pp. 1533-1542 ◽  
Author(s):  
Peter R. Patrylo ◽  
Dennis D. Spencer ◽  
Anne Williamson
Keyword(s):  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Gaba Uptake ◽  
Mesial Temporal Sclerosis ◽  
Gaba Transporter ◽  
Gaba Transporters ◽  
Inhibitory Tone

In vivo dialysis and in vitro electrophysiological studies suggest that GABA uptake is altered in the dentate gyrus of human temporal lobe epileptics characterized with mesial temporal sclerosis (MTLE). Concordantly, anatomical studies have shown that the pattern of GABA-transporter immunoreactivity is also altered in this region. This decrease in GABA uptake, presumably due to a change in the GABA transporter system, may help preserve inhibitory tone interictally. However, transporter reversal can also occur under several conditions, including elevations in [K+]o, which occurs during seizures. Thus GABA transporters could contribute to seizure termination and propagation through heterotransport. To test whether GABA transport is compromised in both the forward (uptake) and reverse (heterotransport) direction in the sclerotic epileptic dentate gyrus, the physiological effects of microapplied GABA and nipecotic acid (NPA; a compound that induces heterotransport) were examined in granule cells in hippocampal slices from kainate (KA)-induced epileptic rats and patients with temporal lobe epilepsy (TLE). GABA- and NPA-induced responses were prolonged in granule cells from epileptic rats versus controls (51.3 and 31.3% increase, respectively) while the conductance change evoked with NPA microapplication was reduced by 40%. Furthermore the ratio of GABA/NPA conductance, but not duration, was significantly >1 in epileptic rats but not controls, suggesting a compromise in transporter function in both directions. Similar changes were observed in tissue resected from epileptic patients with medial temporal sclerosis but not in those without the anatomical changes associated with MTLE. These data suggest that the GABA transporter system is functionally compromised in both the forward and reverse directions in the dentate gyrus of chronically epileptic tissue characterized by mesial temporal sclerosis. This alteration may enhance inhibitory tone interically yet be permissive for seizure propagation due to a decreased probability for GABA heterotransport during seizures.

Differential Modulation of CA1 and Dentate Gyrus Interneurons During Exploration of Novel Environments

2004 ◽  
Vol 91 (2) ◽  
pp. 863-872 ◽  
Author(s):  
Douglas Nitz ◽  
Bruce McNaughton
Keyword(s):  
Dentate Gyrus ◽  
Spatial Information ◽  
Specific Activity ◽  
Activity Patterns ◽  
Spatial Location ◽  
The Novel ◽  
Novel Environment ◽  
Principal Cells ◽  
Familiar Environment ◽  
Novel Environments

Parallel recordings of hippocampal principal cells and interneurons were obtained as rats foraged in familiar and adjacent, novel environments. Firing rates of each cell type were assessed as a function of spatial location. Many CA1 interneurons exhibited large decreases in activity in the novel compared with the familiar environment. Dentate gyrus interneurons, however, were much more likely to exhibit large increases in firing in the novel environment. Neither effect was correlated with basic interneuron discharge properties such as degree of theta modulation, baseline firing rate or degree of spatially modulated discharge. Both CA1 and dentate gyrus interneuron rate changes extended into regions of the familiar environment bordering the novel environment. Principal cells in CA1 and dentate gyrus exhibited similar patterns of place specific activity each being indicative of incorporation of novel spatial information into the spatial representation of the familiar environment. The data indicate that inhibitory networks in the CA1 and dentate gyrus areas are modulated in a divergent fashion during the acquisition of novel spatial information and that interneuron activities can be used to detect those regions of an environment subject to redistribution of principal cell spatial activity patterns.

scholarly journals Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus

Science ◽  
2019 ◽  
Vol 364 (6440) ◽  
pp. 578-583 ◽  
Author(s):  
Victor M. Luna ◽  
Christoph Anacker ◽  
Nesha S. Burghardt ◽  
Hameda Khandaker ◽  
Valentine Andreu ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Spatial Information ◽  
Granule Cells ◽  
Contextual Information ◽  
Critical Function ◽  
Metabotropic Glutamate ◽  
Monosynaptic Inhibition

Young adult-born granule cells (abGCs) in the dentate gyrus (DG) have a profound impact on cognition and mood. However, it remains unclear how abGCs distinctively contribute to local DG information processing. We found that the actions of abGCs in the DG depend on the origin of incoming afferents. In response to lateral entorhinal cortex (LEC) inputs, abGCs exert monosynaptic inhibition of mature granule cells (mGCs) through group II metabotropic glutamate receptors. By contrast, in response to medial entorhinal cortex (MEC) inputs, abGCs directly excite mGCs throughN-methyl-d-aspartate receptors. Thus, a critical function of abGCs may be to regulate the relative synaptic strengths of LEC-driven contextual information versus MEC-driven spatial information to shape distinct neural representations in the DG.

scholarly journals Parallel processing of sensory cue and spatial information in the Dentate Gyrus

2020 ◽  
Author(s):  
Sebnem N. Tuncdemir ◽  
Andres D. Grosmark ◽  
Gergely Turi ◽  
Amei Shank ◽  
Jack Bowler ◽  
...  
Keyword(s):  
Parallel Processing ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Spatial Information ◽  
Granule Cells ◽  
Spatial Location ◽  
Place Cells ◽  
On Line ◽  
Sensory Cue ◽  
Self Motion

AbstractDuring exploration, animals form an internal map of an environment by combining information about specific sensory cues or landmarks with the animal’s motion through space, a process which critically depends on the mammalian hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal trisynaptic circuit where self-motion and sensory cue information are integrated, yet it remains unknown how neurons within the DG encode both cue related (“what”) and spatial (“where”) information during cognitive map formation. Using two photon calcium imaging in head fixed mice running on a treadmill, along with on-line sensory cue manipulation at specific track locations, we have identified robust sensory cue responses in DG granule cells largely independent of spatial location. Granule cell cue responses are stable for long periods of time, selective for the modality of the stimulus and accompanied by strong inhibition of the firing of other active neurons. At the same time, there is a smaller fraction of neurons whose firing is spatially tuned but insensitive to the presentation of nearby cues, similar to traditional place cells. These results demonstrate the existence of “cue cells” in addition to the better characterized “place cells” in the DG, an important heterogeneity that has been previously overlooked. We hypothesize that the observed diversity of representations within the granule cell population may support parallel processing of complementary sensory and spatial information and impact the role of the dentate gyrus in spatial navigation and episodic memory.

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