Towards a functional organization of the medial temporal lobe memory system: Role of the parahippocampal and medial entorhinal cortical areas

Eichenbaum, Howard; Lipton, Paul A.

doi:10.1002/hipo.20500

Cited by 179 publications

(160 citation statements)

References 104 publications

(129 reference statements)

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“…In contrast, with reset of phase at reward locations, simulated entorhinal neurons show context-dependent firing on the stem that differs between the left-to-right trajectory and the right-to-left trajectory, as shown in Figure 5B (left). This is consistent with physiological recordings showing context-dependent entorhinal activity during this task (Lipton et al, 2007;Eichenbaum and Lipton, 2008). The input from these entorhinal neurons results in context-dependent firing of hippocampal neurons on different trajectories, as shown in Figure 5B (right).…”

Section: Continuous Spatial Alternationsupporting

confidence: 89%

Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting

2008

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ABSTRACT:This article presents a model of grid cell firing based on the intrinsic persistent firing shown experimentally in neurons of entorhinal cortex. In this model, the mechanism of persistent firing allows individual neurons to hold a stable baseline firing frequency. Depolarizing input from speed-modulated head direction cells transiently shifts the frequency of firing from baseline, resulting in a shift in spiking phase in proportion to the integral of velocity. The convergence of input from different persistent firing neurons causes spiking in a grid cell only when the persistent firing neurons are within similar phase ranges. This model effectively simulates the two-dimensional firing of grid cells in open field environments, as well as the properties of theta phase precession. This model provides an alternate implementation of oscillatory interference models. The persistent firing could also interact on a circuit level with rhythmic inhibition and neurons showing membrane potential oscillations to code position with spiking phase. These mechanisms could operate in parallel with computation of position from visual angle and distance of stimuli. In addition to simulating two-dimensional grid patterns, models of phase interference can account for context-dependent firing in other tasks. In network simulations of entorhinal cortex, hippocampus, and postsubiculum, the reset of phase effectively replicates context-dependent firing by entorhinal and hippocampal neurons during performance of a continuous spatial alternation task, a delayed spatial alternation task with running in a wheel during the delay period (Pastalkova et al., Science, 2008), and a hairpin maze task.

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Section: Continuous Spatial Alternationsupporting

confidence: 89%

Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting

2008

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“…The parahippocampal region along with the hippocampus and association areas of the cerebral cortex form the medial temporal lobe system (Eichenbaum & Lipton, 2008). There is a bidirectional hierarchy of reciprocal connections in which the cortical association areas connect to the parahippocampal region and in turn to the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…There is a bidirectional hierarchy of reciprocal connections in which the cortical association areas connect to the parahippocampal region and in turn to the hippocampus. The output from the hippocampus is then returned to the parahippocampal region and to the cortical regions where the input originated (Eichenbaum & Lipton, 2008). The parahippocampal region is associated with contextual associations or episodic memory and shows a familiarity effect during repetition of tasks, with greater activation during novel as compared with familiar tasks (O'Kane et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Neural effects of cognitive–behavioural therapy on dysfunctional attitudes in depression

et al. 2014

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Background. Dysfunctional attitudes are a feature of depression that has been correlated with receptor binding abnormalities in limbic and cortical regions. We sought to investigate the functional neuroanatomy of dysfunctional attitudes in major depressive disorder (MDD) and the effects of treatment with cognitive-behavioural therapy (CBT).Method. Participants were 16 patients with unipolar depression in an acute depressive episode (mean age 40.0 years) and 16 matched healthy controls (mean age 39.9 years). Patients were medication free and received a course of treatment with CBT. All participants underwent functional magnetic resonance imaging (fMRI) scans at baseline and at week 16, prior to the initiation of therapy and following the course of CBT for patients. During each fMRI scan, participants indicated their attributions to statements from a modified Dysfunctional Attitudes Scale (mDAS-48).Results. MDD patients in an acute depressive episode endorsed a greater number of extreme responses to DAS statements, which normalized following CBT treatment. Extreme attributions were associated with greater activation in the left hippocampal region, inferior parietal lobe and precuneus in MDD patients as compared with healthy controls as a main effect of group. An interaction effect was found in the left parahippocampal region, which showed less attenuation in MDD patients at the follow-up scan relative to healthy controls.Conclusions. Attenuation of activity in the parahippocampal region may be indicative of an improvement in dysfunctional thinking following CBT treatment in depression, while persistent engagement of regions involved in attentional processing and memory retrieval with extreme attributions reflects a trait feature of depression.

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“…The entorhinalhippocampus system is known to play an important role in the formation and consolidation of memories, particularly spatial memories [36][37][38]. Among the brain regions surveyed, we found the highest content of OR TBI biomarkers in the hippocampal formation, with relatively lower levels of OR TBI expression in the entorhinal cortex.…”

Section: Discussionmentioning

confidence: 63%

Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer's Disease

Pasinetti¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEOct PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERIcahn School of Medicine at Mount Sinai 1 Gustave L. Levy Place New York, NY 10029 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTTraumatic Brain Injury (TBI) is a risk factor for subsequent development of Alzheimer's disease (AD). Abnormal tau processing is a common pathological feature of TBI and AD and tau neuropathology plays a key role in both TBI complications and AD dementia. This study is based on our recent findings of aberrant down-regulation of specific olfactory receptors (OR) as biological indices for TBI and down-regulation of OR TBI biomarkers following TBI might contribute to TBI-related tau neuropathology. We propose that down-regulation of select OR TBI biomarkers in the brain may contribute to the elevation of tau neuropathological phenotypes, thereby promoting the development of AD dementia among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans with exposure to TBI. In Year 1, we found that activation of OR4M1 by a low affinity ligand resulted in reduced tau phosphorylation via JNK signaling pathway and a manuscript was published based on this finding. We constructed a virtual 3D structure model for OR4M1 to screen high affinity ligands. Fifty Seven (57) compounds were identified and clustered into 32 clusters based on their structure similarities. We found significant decrease of the blood OR contents in a rat model of TBI. Outcomes from our study will provide a better understanding of TBI complications and how it is related to AD. (Zhao et al., 2013). In addition, we found down-regulation of these ORs is significantly correlated with the severity of brain injury and TBI-specific symptoms, and a two-biomarker panel, comprised of OR11H1 and OR4M1, provides the best criterion for segregating the ...

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Towards a functional organization of the medial temporal lobe memory system: Role of the parahippocampal and medial entorhinal cortical areas

Cited by 179 publications

References 104 publications

Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting

Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting

Neural effects of cognitive–behavioural therapy on dysfunctional attitudes in depression

Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer's Disease

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