Parallel processing streams in the hippocampus

Lee, Hee-Kyung; GoodSmith, Douglas; Knierim, James

doi:10.1016/j.conb.2020.03.004

Cited by 56 publications

(68 citation statements)

References 70 publications

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“…6C). Although pattern completion and pattern separation are often presented as competing processes that produce a single output, we have argued previously that the gradients along the CA3 transverse axis might allow the system to output simultaneously a pattern-separated output (from proximal CA3 through distal CA1) and a pattern-completed output (from distal CA3 through proximal CA1) (Lee et al, 2020). Distal CA1 is associated with the LEC and proximal CA1 is associated with the MEC.…”

Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 98%

“…However, the present data are somewhat inconsistent with this view, because the part of CA3 that appears to underlie pattern completion (distal CA3) does not show hyperactivity in aged rats, and may even show hypoactivity. Instead, the part of CA3 that shows hyperactivity is the region that, along with the dentate gyrus, is involved in pattern separation (GoodSmith et al, 2019;Lee et al, 2020Lee et al, , 2015Lu et al, 2015). Thus, using the logic of Wilson et al (2006), a simple model might suggest that aged subjects should show greater pattern separation due to the hyperactivity specific to proximal CA3.…”

Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 99%

“…Thus, using the logic of Wilson et al (2006), a simple model might suggest that aged subjects should show greater pattern separation due to the hyperactivity specific to proximal CA3. However, considering the complex anatomy and parallel processing streams throughout the hippocampal transverse axis (Lee et al, 2020), we propose a revised model that presents a more nuanced view of how the patterns of hyperactivity and potential hypoactivity along the transverse axis of aged rats may result in an imbalance of the pattern-completion/pattern-separation balance. In this revised model, the bias toward pattern completion in aged rats results less from an enhancement of pattern completion, as suggested by Wilson et al (2006), but rather from a weakening of pattern separation.…”

Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 99%

“…Functional gradients along the CA3 transverse axis suggest that proximal CA3, in conjunction with the dentate gyrus, supports pattern separation and distal CA3, with its extensive, recurrent collateral system, supports pattern completion (Lee et al, 2015;Lu et al, 2015). Proximal and distal CA3 send topographically organized projections to distal and proximal CA1, respectively, to form functionally distinct, parallel processing streams along the transverse axis in the hippocampal circuit (Amaral and Witter, 1989;Ishizuka et al, 1995;Lee et al, 2020). While age-related memory impairments have been linked to CA3 hyperactivity and enhanced pattern completion (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Lee

Wang

Zeger

et al. 2020

Preprint

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Age-related memory deficits are correlated with neural hyperactivity in the CA1 and CA3 regions of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between the normal tradeoff between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from male young and aged Long-Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite trend, with a decreasing gradient from proximal to distal CA3. Thus, CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared to young rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus, the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote bistable representations under certain conditions.

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Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 98%

Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 99%

Section: Role Of Aging Ca3 In Pattern Separation and Pattern Completionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Lee

Wang

Zeger

et al. 2020

Preprint

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“…Entorhino-dentate axons relay cortical information from the entorhinal cortex (EC) to the dentate gyrus (DG;e.g., Van Hoesen et al, 1972;Wilson and Steward, 1978;Jones, 1993;Förster et al, 2006;Nilssen et al, 2019;Lee et al, 2020). Anatomically, the entorhino-dentate connections are subdivided into two major projections: one projection arises from layer II neurons in the medial entorhinal cortex (MEC) and its axons terminate in the middle molecular layer of the DG.…”

Section: Introductionmentioning

confidence: 99%

Crossed Entorhino-Dentate Projections Form and Terminate With Correct Layer-Specificity in Organotypic Slice Cultures of the Mouse Hippocampus

et al. 2021

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The entorhino-dentate projection, i.e., the perforant pathway, terminates in a highly ordered and laminated fashion in the rodent dentate gyrus (DG): fibers arising from the medial entorhinal cortex (MEC) terminate in the middle molecular layer, whereas fibers arising from the lateral entorhinal cortex (LEC) terminate in the outer molecular layer of the DG. In rats and rabbits, a crossed entorhino-dentate projection exists, which originates from the entorhinal cortex (EC) and terminates in the contralateral DG. In contrast, in mice, such a crossed projection is reportedly absent. Using single and double mouse organotypic entorhino-hippocampal slice cultures, we studied the ipsi- and crossed entorhino-dentate projections. Viral tracing revealed that entorhino-dentate projections terminate with a high degree of lamina-specificity in single as well as in double cultures. Furthermore, in double cultures, entorhinal axons arising from one slice freely intermingled with entorhinal axons originating from the other slice. In single as well as in double cultures, entorhinal axons exhibited a correct topographical projection to the DG: medial entorhinal axons terminated in the middle and lateral entorhinal axons terminated in the outer molecular layer. Finally, entorhinal neurons were virally transduced with Channelrhodopsin2-YFP and stimulated with light, revealing functional connections between the EC and dentate granule cells. We conclude from our findings that entorhino-dentate projections form bilaterally in the mouse hippocampus in vitro and that the mouse DG provides a permissive environment for crossed entorhinal fibers.

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Measuring Pattern Separation in Hippocampus by in Situ Hybridization

Eom

Lee

2022

Current Protocols

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Distinguishing different contexts is thought to involve a form of pattern separation that minimizes overlap between neural ensembles representing similar experiences. Theoretical models suggest that the dentate gyrus (DG) segregates cortical input patterns before relaying its discriminated output patterns to the CA3 hippocampal field. This suggests that the evaluation of neural ensembles in DG and CA3 could be an important means to investigate the process of pattern separation. In the past, measurement of entorhinal cortex (EC), DG, and CA3 ensembles was largely dependent upon in vivo electrophysiological recording, which is technically difficult. This protocol provides a method to instead measure pattern separation by a molecular method that provides direct spatial resolution at the cellular level.

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Parallel processing streams in the hippocampus

Cited by 56 publications

References 70 publications

Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Crossed Entorhino-Dentate Projections Form and Terminate With Correct Layer-Specificity in Organotypic Slice Cultures of the Mouse Hippocampus

Measuring Pattern Separation in Hippocampus by in Situ Hybridization

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