scholarly journals Hippocampal ensemble dynamics timestamp events in long-term memory

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Alon Rubin ◽  
Nitzan Geva ◽  
Liron Sheintuch ◽  
Yaniv Ziv

The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ugur Dag ◽  
Zhengchang Lei ◽  
Jasmine Q Le ◽  
Allan Wong ◽  
Daniel Bushey ◽  
...  

Animals consolidate some, but not all, learning experiences into long-term memory. Across the animal kingdom, sleep has been found to have a beneficial effect on the consolidation of recently formed memories into long-term storage. However, the underlying mechanisms of sleep dependent memory consolidation are poorly understood. Here, we show that consolidation of courtship long-term memory in Drosophila is mediated by reactivation during sleep of dopaminergic neurons that were earlier involved in memory acquisition. We identify specific fan-shaped body neurons that induce sleep after the learning experience and activate dopaminergic neurons for memory consolidation. Thus, we provide a direct link between sleep, neuronal reactivation of dopaminergic neurons, and memory consolidation.


2001 ◽  
Vol 24 (1) ◽  
pp. 114-115 ◽  
Author(s):  
S. E. Avons ◽  
Geoff Ward ◽  
Riccardo Russo

The empirical data do not unequivocally support a consistent fixed capacity of four chunks. We propose an alternative account whereby capacity is limited by the precision of specifying the temporal and spatial context in which items appear, that similar psychophysical constraints limit number estimation, and that short term memory (STM) is continuous with long term memory (LTM).


2012 ◽  
Vol 2012 (3) ◽  
pp. pdb.prot068239-pdb.prot068239 ◽  
Author(s):  
S. Kaech ◽  
C.-F. Huang ◽  
G. Banker

2001 ◽  
Vol 356 (1413) ◽  
pp. 1493-1503 ◽  
Author(s):  
Neil Burgess ◽  
Suzanna Becker ◽  
John A. King ◽  
John O'Keefe

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time–limited store supporting neocortical long–term memory; and (iii) a content–addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read–out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural–level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real–life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long–term storage while parietal egocentric representations are used to imagine, manipulate and re–experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez's circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life–like events in virtual reality provides support for the model's functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.


2014 ◽  
Vol 111 (1) ◽  
pp. 208-216 ◽  
Author(s):  
Naoko Nishiyama ◽  
Jeremy Colonna ◽  
Elise Shen ◽  
Jennifer Carrillo ◽  
Hiroshi Nishiyama

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and well-defined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ∼80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.


2019 ◽  
Author(s):  
Ellen D. Witkowski ◽  
Şefik Evren Erdener ◽  
Kıvılcım Kılıç ◽  
Sreekanth Kura ◽  
Jianbo Tang ◽  
...  

AbstractTraumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.


2017 ◽  
Vol 114 (38) ◽  
pp. E8062-E8071 ◽  
Author(s):  
Amy R. Poe ◽  
Lingfeng Tang ◽  
Bei Wang ◽  
Yun Li ◽  
Maria L. Sapar ◽  
...  

Neurons sometimes completely fill available space in their receptive fields with evenly spaced dendrites to uniformly sample sensory or synaptic information. The mechanisms that enable neurons to sense and innervate all space in their target tissues are poorly understood. UsingDrosophilasomatosensory neurons as a model, we show that heparan sulfate proteoglycans (HSPGs) Dally and Syndecan on the surface of epidermal cells act as local permissive signals for the dendritic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the entire skin. Using long-term time-lapse imaging with intactDrosophilalarvae, we found that dendrites grow into HSPG-deficient areas but fail to stay there. HSPGs are necessary to stabilize microtubules in newly formed high-order dendrites. In contrast to C4da neurons, non–space-filling sensory neurons that develop in the same microenvironment do not rely on HSPGs for their dendritic growth. Furthermore, HSPGs do not act by transporting extracellular diffusible ligands or require leukocyte antigen-related (Lar), a receptor protein tyrosine phosphatase (RPTP) and the only knownDrosophilaHSPG receptor, for promoting dendritic growth of space-filling neurons. Interestingly, another RPTP, Ptp69D, promotes dendritic growth of C4da neurons in parallel to HSPGs. Together, our data reveal an HSPG-dependent pathway that specifically allows dendrites of space-filling neurons to innervate all target tissues inDrosophila.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Smitha Karunakaran

AbstractIn this study we demonstrate that 2 month old APPswe/PS1dE9 mice, a transgenic model of Alzheimer’s disease, exhibited intact short-term memory in Pavlovian hippocampal—dependent contextual fear learning task. However, their long-term memory was impaired. Intra-CA1 infusion of isoproterenol hydrochloride, the β-adrenoceptor agonist, to the ventral hippocampus of APPswe/PS1dE9 mice immediately before fear conditioning restored long-term contextual fear memory. Infusion of the β-adrenoceptor agonist + 2.5 h after fear conditioning only partially rescued the fear memory, whereas infusion at + 12 h post conditioning did not interfere with long-term memory persistence in this mouse model. Furthermore, Intra-CA1 infusion of propranolol, the β-adrenoceptor antagonist, administered immediately before conditioning to their wildtype counterpart impaired long-term fear memory, while it was ineffective when administered + 4 h and + 12 h post conditioning. Our results indicate that, long-term fear memory persistence is determined by a unique β-adrenoceptor sensitive time window between 0 and + 2.5 h upon learning acquisition, in the ventral hippocampal CA1 of APPswe/PS1dE9 mice. On the contrary, β-adrenoceptor agonist delivery to ventral hippocampal CA1 per se did not enhance innate anxiety behaviour in open field test. Thus we conclude that, activation of learning dependent early β-adrenoceptor modulation underlies and is necessary to promote long-term fear memory persistence in APPswe/PS1dE9.


2015 ◽  
Vol 2 (6) ◽  
pp. 150031 ◽  
Author(s):  
Dirk Saalfrank ◽  
Anil Krishna Konduri ◽  
Shahrzad Latifi ◽  
Rouhollah Habibey ◽  
Asiyeh Golabchi ◽  
...  

Most in vitro electrophysiology studies extract information and draw conclusions from representative, temporally limited snapshot experiments. This approach bears the risk of missing decisive moments that may make a difference in our understanding of physiological events. This feasibility study presents a simple benchtop cell-culture perfusion system adapted to commercial microelectrode arrays (MEAs), multichannel electrophysiology equipment and common inverted microscopy stages for simultaneous and uninterrupted extracellular electrophysiology and time-lapse imaging at ambient CO 2 levels. The concept relies on a transparent, replica-casted polydimethylsiloxane perfusion cap, gravity- or syringe-pump-driven perfusion and preconditioning of pH-buffered serum-free cell-culture medium to ambient CO 2 levels at physiological temperatures. The low-cost microfluidic in vitro enabling platform, which allows us to image cultures immediately after cell plating, is easy to reproduce and is adaptable to the geometries of different cell-culture containers. It permits the continuous and simultaneous multimodal long-term acquisition or manipulation of optical and electrophysiological parameter sets, thereby considerably widening the range of experimental possibilities. Two exemplary proof-of-concept long-term MEA studies on hippocampal networks illustrate system performance. Continuous extracellular recordings over a period of up to 70 days revealed details on both sudden and gradual neural activity changes in maturing cell ensembles with large intra-day fluctuations. Correlated time-lapse imaging unveiled rather static macroscopic network architectures with previously unreported local morphological oscillations on the timescale of minutes.


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