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.

The role of the dentate gyrus in mnemonic functions

Neuroforum ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jonas-Frederic Sauer ◽  
Marlene Bartos
Keyword(s):  
Dentate Gyrus ◽  
Memory Formation ◽  
Population Activity ◽  
Two Photon ◽  
Select Group ◽  
Cell Association ◽  
Mechanisms Of Memory ◽  
Input Gate

AbstractThe hippocampus is decisive for the storage of conscious memories. Current theories suggest that experience-dependent modifications in excitation–inhibition balance enable a select group of neurons to form a new cell association during learning which represents the new memory trace. It was further proposed that particularly GABAergic-inhibitory interneurons have a large impact on population activity in neuronal networks by means of their inhibitory output synapses. They synchronize active principal cells at high frequencies, thereby supporting their binding to cell assemblies to jointly encode information. However, how cell associations emerge in space and time and how interneurons may contribute to this process is still largely unknown. We started to address this fundamental question in the dentate gyrus (DG) as the input gate of the hippocampus, which has an indispensable role in conscious memory formation. We used a combination of in vivo chronic two-photon imaging of population activity in the DG and the hippocampal areas CA1–3 of mice exposed to a virtual reality, in which they perform a goal-oriented spatial memory tasks, with high-density in vivo recordings and multiple whole-cell recordings in acute slice preparations, to determine how memory engrams emerge during learning. We further examine how GABAergic interneurons may contribute to this process. We believe that these lines of research will add to a better understanding on the mechanisms of memory formation in cortical networks.

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 Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

2018 ◽  
Vol 25 (11) ◽  
pp. 2832-2843 ◽  
Author(s):  
Amir Segev ◽  
Masaya Yanagi ◽  
Daniel Scott ◽  
Sarah A. Southcott ◽  
Jacob M. Lister ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Model Systems ◽  
Memory Processing ◽  
Hippocampal Subfields ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Activity

Abstract Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.

Functional Integration of Adult-Generated Granule Cells into Hippocampal Memory

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Tsuyuoshi
Keyword(s):  
Dentate Gyrus ◽  
Water Maze ◽  
Granule Cells ◽  
Functional Integration ◽  
Critical Role ◽  
Memory Formation ◽  
Dependent Manner ◽  
Multiple Forms ◽  
Memory Circuits ◽  
Genetic And Environmental Factors

Throughout adulthood new neurons are continuously added to the dentate gyrus, a hippocampal sub-region that plays a critical role in learning. Our recent studies have used immunohistochemical approaches to visualize the recruitment of these new neurons into circuits supporting water maze memories in intact animals. We showed that functional integration of these adult-generated granule cells into memory circuits proceeds in a maturation-dependent manner, with new granule cells not contributing in significant numbers until they are 4 weeks or older in age. Our current studies are designed to define the range of conditions under which adult-generated granule cells contribute to hippocampal memory formation and focus, in particular, on three issues. First, the hippocampus is involved in multiple forms of spatial and non-spatial memory: Does integration depend upon the type of memory being formed? Second, levels of adult neurogenesis decline exponentially with age and are regulated by a large number of genetic and environmental factors: Does the availability of new neurons affect their rate of incorporation? Third, the dentate gyrus is composed of neurons generated embyonically and postnatally, as well as those throughout adulthood: Are developmentally- and adult-generated neurons incorporated into memory networks at the same or different rates?

scholarly journals Nicotinic Receptors on Local Circuit Neurons in Dentate Gyrus: A Potential Role in Regulation of Granule Cell Excitability

2003 ◽  
Vol 89 (6) ◽  
pp. 3018-3028 ◽  
Author(s):  
Charles J. Frazier ◽  
Ben W. Strowbridge ◽  
Roger L. Papke
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Cell Function ◽  
Granule Cells ◽  
Molecular Layer ◽  
Patch Clamp Recording ◽  
Afferent Pathways ◽  
Age Related

Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole cell patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic α7-containing nicotinic acetylcholine receptors (nAChRs) on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principal neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of ACh in the presence of atropine. We also demonstrate that cholinergic activation of α7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of α7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction and disorders involving regulation of excitability, such as temporal lobe epilepsy.

Burst characteristics of dentate gyrus granule cells: evidence for endogenous and nonsynaptic properties

1996 ◽  
Vol 75 (1) ◽  
pp. 124-132 ◽  
Author(s):  
E. Pan ◽  
J. L. Stringer
Keyword(s):  
Dentate Gyrus ◽  
Action Potentials ◽  
Granule Cells ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Current Injection ◽  
Single Action ◽  
Epileptiform Discharges

1. Hippocampal slices bathed in 8 mM potassium and 0-added calcium exhibited spontaneous epileptiform activity in the dentate gyrus. Extracellular recording revealed recurrent prolonged bursts of population spikes and an associated negative DC shift. These episodes were very similar to the in vivo phenomenon termed maximal dentate activation (MDA). Therefore this in vitro activity will be referred to as MDA-like activity or events. 2. During the MDA-like activity, the individual granule cells exhibited a sustained depolarization that matched the duration of the negative extracellular DC shift. At the beginning of the MDA-like activity, there was a burst of action potentials. After the burst, most granule cells either continued to fire action potentials regularly or in bursts. Some cells exhibited this initial burst of activity and then a dramatic reduction in firing rate. This reduction in rate was followed by a gradual increase in the amplitude and frequency of the epileptiform activity recorded during the remainder of the MDA-like event. 3. Before and between MDA-like events, spontaneous cellular activity consisted of single action potentials and bursts of action potentials on a depolarizing envelope. In addition, depolarizing potentials, up to 13 mV, were recorded. There were no extracellular field potentials associated with these intracellularly recorded potentials. 4. In the 8 mM potassium, 0-added calcium test solution, the membrane potential threshold for burst production was significantly lower than in normal potassium and calcium medium. 5. The effect of depolarizing and hyperpolarizing current injections on the amplitude and frequency of the epileptiform activity was tested. Current injection had no effect on the frequency of the epileptiform activity recorded during the MDA-like events. However, the frequency of the cellular bursts between MDA-like events was very sensitive to current injection. Depolarizing current increased the frequency, and hyperpolarizing current decreased the frequency of the spontaneous activity. 6. This study has shown that in 8 mM potassium and 0-added calcium the granule cells of the dentate gyrus are capable of generating spontaneous bursts that appear to be mediated by endogenous mechanisms. In addition, synchronized epileptiform discharges were recorded from the granule cells at regular intervals that appear were recorded from the granule cells at regular intervals that appear to be mediated by exogenous nonsynaptic mechanisms.

In Vivo Recordings of Long-Term Potentiation and Long-Term Depression in the Dentate Gyrus of the Neonatal Rat

2004 ◽  
Vol 91 (2) ◽  
pp. 613-622 ◽  
Author(s):  
Michael P. O'Boyle ◽  
Viet Do ◽  
Brian E. Derrick ◽  
Brenda J. Claiborne
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Neonatal Rat ◽  
Perforant Path ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Old Rats

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist ( R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.

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