scholarly journals Dentate gyrus population activity during immobility supports formation of precise memories

2020 ◽  
Author(s):  
Martin Pofahl ◽  
Negar Nikbakht ◽  
André N. Haubrich ◽  
Theresa Nguyen ◽  
Nicola Masala ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Granule Cells ◽  
Activity Patterns ◽  
Cell Activity ◽  
Sensory Information ◽  
Population Activity ◽  
Hippocampus Proper ◽  
Spatial Memories

AbstractThe hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in-vivo two-photon Ca2+ imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they recapitulate population patterns evoked during self-motion. Using optogenetic inhibition during immobility, we show that granule cell activity during immobility is required to form dentate gyrus-dependent spatial memories. These data suggest that memory formation is supported by dentate gyrus replay of population codes of the current environment.

scholarly journals Synchronous activity patterns in the dentate gyrus during immobility

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Martin Pofahl ◽  
Negar Nikbakht ◽  
André N Haubrich ◽  
Theresa M Nguyen ◽  
Nicola Masala ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Granule Cells ◽  
Activity Patterns ◽  
Cell Activity ◽  
Sensory Information ◽  
Hippocampus Proper ◽  
Spatial Memories ◽  
Self Motion

The hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in-vivo two-photon Ca2+ imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they are more similar than expected by chance to population patterns evoked during self-motion. Using optogenetic inhibition, we show that granule cell activity is not only required during exploration, but also during immobility in order to form dentate gyrus-dependent spatial memories.

scholarly journals Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Information Transfer ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Dentate Granule Cells ◽  
Hippocampus Proper ◽  
Receptor Plasticity ◽  
Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

scholarly journals A synaptic novelty signal in the dentate gyrus supports switching hippocampal attractor networks from generalization to discrimination

2021 ◽  
Author(s):  
Ruy Gómez-Ocádiz ◽  
Massimiliano Trippa ◽  
Lorenzo Posani ◽  
Simona Cocco ◽  
Rémi Monasson ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Virtual Environments ◽  
Acetylcholine Receptors ◽  
Granule Cells ◽  
Memory Formation ◽  
Synaptic Response ◽  
Population Activity ◽  
Attractor Networks ◽  
Whole Cell Patch Clamp

AbstractEpisodic memory formation and recall are complementary processes that put conflicting requirements on neuronal computations in the hippocampus. How this challenge is resolved in hippocampal circuits is unclear. To address this question, we obtained in vivo whole-cell patch-clamp recordings from dentate gyrus granule cells in head-fixed mice navigating in familiar and novel virtual environments. We find that granule cells consistently show a small transient depolarization of their membrane potential upon transition to a novel environment. This synaptic novelty signal is sensitive to local application of atropine, indicating that it depends on metabotropic acetylcholine receptors. A computational model suggests that the observed transient synaptic response to novel environments may lead to a bias in the granule cell population activity, which can in turn drive the downstream attractor networks to a new state, thereby favoring the switch from generalization to discrimination when faced with novelty. Such a novelty-driven cholinergic switch may enable flexible encoding of new memories while preserving stable retrieval of familiar ones.

Feedforward Inhibition Controls the Spread of Granule Cell–Induced Purkinje Cell Activity in the Cerebellar Cortex

2007 ◽  
Vol 97 (1) ◽  
pp. 248-263 ◽  
Author(s):  
Fidel Santamaria ◽  
Patrick G. Tripp ◽  
James M. Bower
Keyword(s):  
Cerebellar Cortex ◽  
Granule Cells ◽  
Functional Organization ◽  
Cerebellar Granule Cells ◽  
Molecular Layer ◽  
Cell Activity ◽  
Excitatory Input ◽  
Cortical Inhibition ◽  
Before And After

Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). Although most theories of cerebellar function assume these synapses produce an excitatory sequential “beamlike” activation of PCs, numerous physiological studies have failed to find such beams. Using a computer model of the cerebellar cortex we predicted that the lack of PCs beams is explained by the concomitant pf activation of feedforward molecular layer inhibition. This prediction was tested, in vivo, by recording PCs sharing a common set of pfs before and after pharmacologically blocking inhibitory inputs. As predicted by the model, pf-induced beams of excitatory PC responses were seen only when inhibition was blocked. Blocking inhibition did not have a significant effect in the excitability of the cerebellar cortex. We conclude that pfs work in concert with feedforward cortical inhibition to regulate the excitability of the PC dendrite without directly influencing PC spiking output. This conclusion requires a significant reassessment of classical interpretations of the functional organization of the cerebellar cortex.

scholarly journals Does a Unique Type of CA3 Pyramidal Cell in Primates Bypass the Dentate Gate?

2005 ◽  
Vol 94 (1) ◽  
pp. 896-900 ◽  
Author(s):  
Paul S. Buckmaster
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Synaptic Input ◽  
Granule Cells ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Dentate Granule Cells ◽  
Excitatory Synaptic Input ◽  
Ca3 Pyramidal Cells

The predominant excitatory synaptic input to the hippocampus arises from entorhinal cortical axons that synapse with dentate granule cells, which in turn synapse with CA3 pyramidal cells.Thus two highly excitable brain areas—the entorhinal cortex and the CA3 field—are separated by dentate granule cells, which have been proposed to function as a gate or filter. However, unlike rats, primates have “dentate” CA3 pyramidal cells with an apical dendrite that extends into the molecular layer of the dentate gyrus, where they could receive strong, monosynaptic, excitatory synaptic input from the entorhinal cortex. To test this possibility, the dentate gyrus molecular layer was stimulated while intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices from neurologically normal macaque monkeys. Stimulus intensity of the outer molecular layer of the dentate gyrus was standardized by the threshold intensity for evoking a dentate gyrus field potential population spike. Recorded proximal CA3 pyramidal cells were labeled with biocytin, processed with diaminobenzidine for visualization, and classified according to their dendritic morphology. In response to stimulation of the dentate gyrus molecular layer, action potential thresholds were similar in proximal CA3 pyramidal cells with different dendritic morphologies. These findings do not support the hypothesis that dentate CA3 pyramidal cells receive stronger synaptic input from the entorhinal cortex than do other proximal CA3 pyramidal cells.

scholarly journals Dentate gyrus formation requires Emx2

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3893-3898 ◽  
Author(s):  
M. Pellegrini ◽  
A. Mansouri ◽  
A. Simeone ◽  
E. Boncinelli ◽  
P. Gruss
Keyword(s):  
Dentate Gyrus ◽  
Early Embryogenesis ◽  
Cerebral Hemispheres ◽  
Limbic Cortex ◽  
Olfactory Bulbs ◽  
Morphological Alterations ◽  
Hippocampus Proper ◽  
The Brain

Emx 1 and 2 are the murine homologues of the Drosophila empty spiracles gene and based on their expression pattern may be involved in the regional specification of the mammalian forebrain. During early embryogenesis, Emx2 is expressed in the presumptive cerebral cortex and olfactory bulbs and later, in the hippocampus proper and dentate gyrus. The latter are involved in memory processes. To understand the role of Emx2 in vivo, we have mutated the gene in mice. Homozygous embryos die postnatally because of severe urogenital alterations. These mice present cerebral hemispheres with a reduced size and exhibit specific morphological alterations in allocortical structures of the medial wall of the brain. The dentate gyrus is missing and the hippocampus proper is reduced. The medial limbic cortex is also severely shortened. The development of the dentate gyrus is affected at the onset of its formation with defects in the neuroepithelium from which it originates. These findings demonstrate that Emx2 is required for the development of several forebrain structures.

scholarly journals The anterior paired lateral neuron normalizes odour-evoked activity at the mushroom body calyx

2021 ◽  
Author(s):  
Luigi Prisco ◽  
Stephan Hubertus Deimel ◽  
Hanna Yeliseyeva ◽  
Andre Fiala ◽  
Gaia Tavosanis
Keyword(s):  
Mushroom Body ◽  
Activity Patterns ◽  
Sensory Information ◽  
Input Circuit ◽  
Projection Neurons ◽  
Neuronal Populations ◽  
Kenyon Cells ◽  
Presynaptic Boutons ◽  
Evoked Activity

To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral neuron (APL) in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic Kenyon cells (KCs). Combining EM data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the Kenyon cells requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.

scholarly journals The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luigi Prisco ◽  
Stephan Hubertus Deimel ◽  
Hanna Yeliseyeva ◽  
André Fiala ◽  
Gaia Tavosanis
Keyword(s):  
Mushroom Body ◽  
Activity Patterns ◽  
Sensory Information ◽  
Input Circuit ◽  
Projection Neurons ◽  
Neuronal Populations ◽  
Kenyon Cells ◽  
Presynaptic Boutons ◽  
Evoked Activity

To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral neuron (APL) in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic Kenyon cells (KCs). Combining EM data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the Kenyon cells requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.

scholarly journals Neuronal networks in the spotlight

e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
F. Helmchen ◽  
M. Hübener
Keyword(s):  
Neuronal Networks ◽  
Neural Circuits ◽  
Calcium Influx ◽  
Fluorescent Proteins ◽  
Activity Patterns ◽  
Cell Activity ◽  
Movement Control ◽  
Dynamic Activity ◽  
Two Photon Microscopy

AbstractThe brain’s astounding achievements regard­ing movement control and sensory process­ing are based on complex spatiotemporal ac­tivity patterns in the relevant neuronal net­works. Our understanding of neuronal net­work activity is, however, still poor, not least because of the experimental difficulties in di­rectly observing neural circuits at work in the living brain (in vivo). Over the last decade, new opportunities have emerged-especial­ly utilizing two-photon microscopy-to in­vestigate neuronal networks in action. Cen­tral to this progress was the development of fluorescent proteins that change their emis­sion depending on cell activity, enabling the visualization of dynamic activity patterns in local neuronal populations. Currently, genet­ically encoded calcium indicators, proteins that indicate neuronal activity based on ac­tion potential-evoked calcium influx, are be­ing increasingly used. Long-term expression of these indicators allows repeated moni­toring of the same neurons over weeks and months, such that the stability and plastici­ty of their functional properties can be char­acterized. Furthermore, permanent indicator expression facilitates the correlation of cel­lular activity patterns and behavior in awake animals. Using examples from recent studies of information processing in the mouse neo­cortex, we review in this article these fasci­nating new possibilities and discuss the great potential of the fluorescent proteins to eluci­date the mysteries of neural circuits.

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