The hippocampus contributes to temporal duration memory in the context of event sequences: A cross-species perspective

Glucose is an essential cellular fuel for maintaining normal brain functions. Traumatic brain injury (TBI) decreases brain glucose utilization in both human and experimental animals during the acute or subacute phase of TBI. It remains unclear as to how the damages affect brain glucose utilization and its association with persistent neurobehavioral impairments in the chronic phase of mild TBI (mTBI). Accordingly, we compared expression of selected genes important to brain glucose utilization in different brain regions of mice during the chronic phase in mTBI vs. sham operated mice. These genes included hexokinase-1 (HK1), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate dehydrogenase (PDH), capillary glucose transporter (Glut-1), neuron glucose transporter (Glut-3), astrocyte lactate transpor1 (MCT-1), neuron lactate transporter (MCT-2), lactate receptor (GPR81), and Hexokinase isoform-2 (HK2). Young adult male C57BL/6J mice were brain injured with repetitive closed-head concussions. Morris water maze (MWM), elevated plus maze (EPM), and neurological severity score test (NSS) were performed for evaluation of mice neurobehavioral impairments at 2, 4, and 6 months post mTBI. Two days after completion of the last behavioral test, the frontal cortex, hippocampus, brainstem, hypothalamus, and cerebellum were collected for gene expression measurements. The expression of the mRNAs encoding PK, and PDH, two critical enzymes in glucose metabolism, was decreased at all-time points only in the hippocampus, but was unchanged in the brainstem, hypothalamus, and cortex in mTBI mice. mTBI mice also exhibited the following behavioral alterations: (1) decreased spatial learning and memory 2, 4, and 6 months after the injury, (2) increased proportion of time spent on open vs. closed arms determined by EPM, and (3) accelerated reduction in motor activity observed at 4 months, two months earlier than observed in the sham group, during the EPM testing. There were no significant differences in NSS between Huynh et al. Chronic Effects of mTBI injury and sham groups at any of the three time points. Thus, mTBI in male mice led to persistent decreased hippocampal expression of mRNAs that encode critical glucose utilization related enzymes in association with long-term impairments in selected neurobehavioral outcomes.

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“…The hippocampus plays a major role in learning and memory (36,37). Aging process has decreased the expressions of majority gene measured.…”

Section: Expression In Hippocampus (Table 2 and Supplemental File 1)mentioning

confidence: 99%

Chronic Neurobehavioral Impairments and Decreased Hippocampal Expression of Genes Important for Brain Glucose Utilization in a Mouse Model of Mild TBI

et al. 2020

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“…The most noticeable progress of our study was its extension of previous knowledge from trace conditioning, electrophysiology, and computational models. First, data from trace conditioning were believed to be evidence of the role of the hippocampus in temporal duration memory (Lee et al, 2019). However, other explanations, such as the disappearance of the memory trace of the CS presentation or an impairment of the "continuation" proposed by the ICAT model of timing (Petter et al, 2016), can also explain the data.…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies have shown that hippocampal dysfunction alters interval timing behavior (for review, Lee, Thavabalasingam, Alushaj, Cavdaroglu, & Ito, 2019). The "classic effects" (Yin & Troger, 2011) of hippocampal or hippocampus-related regions dysfunctions on interval timing are to alter the accuracy (the length of the estimated or "subjective" durations) in the peak-interval (PI) procedure (Hata & Okaichi, 1998;Meck, 1988;Meck, Church, & Olton, 1984;Olton Meck, & Church, 1987;Tam, Jennings, & Bonardi, 2015;Yin & Meck, 2014) and the differential reinforcement of low rate (DRL) schedules (Jaldow & Oakley, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…Many studies using CS offset -US onset intervals (CS-US intervals) in the seconds range (i.e., range of the interval timing) have reported that hippocampal lesions, especially on the dorsal parts, impair the acquisition and retention of trace fear conditioning (McEchron, Bouwmeester, Tseng, Weiss, & Disterhoft, 1998;McEchron, Tseng, & Disterhoft, 2000;Quinn, Oommen, Morrison, & Fanselow, 2002;Quinn, Loya, Ma, & Fanselow, 2005;Lin & Honey, 2011;Raybuck & Lattal, 2011;Sellami, Abed, Brayda-Bruno, Etchamendy, Valério, Oulé, … Marighetto, 2017). Lee et al (2019) stated that trace conditioning studies largely substantiate the hippocampus in representations of temporal duration memory. The hippocampal "time cell," which fires at a specific moment in a temporally structured experience, has received much attention in the last decade (Pastalkova, Itskov, Amarasingham, & Buzsaki, 2008;MacDonald, Carrow, Place, & Eichenbaum, 2013;Saltz, Tiganj, Khasnabish, Kohley, Sheehan, Howard, & Eichenbaum, 2016; for review, Eichenbaum, 2014).…”

Section: Introductionmentioning

confidence: 99%

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The dorsal hippocampus is required for the formation of long-term duration memories in rats

Hata

Yamashita

Kamada

2020

Preprint

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Interval timing—the perception of durations mainly in seconds or minutes—is a ubiquitous behavior in organisms. Animal studies have suggested that the hippocampus plays an essential role in duration memory; however, the memory processes involved are unclear. To clarify the role of the dorsal hippocampus in the acquisition of long-term duration memories, we adapted the “time-shift paradigm” to a peak-interval procedure. After a sufficient number of training sessions with an initial target duration (20 s), the rats underwent “shift sessions” with a new target duration (40 s) under a muscimol (0.5 µg per side) infusion into the bilateral dorsal hippocampus. The memory of the new target duration was then tested in drug-free “probe sessions,” including the empty trials in which any lever presses were not reinforced. In the probe sessions, the mean peak function of the muscimol group was located leftward to the control group, but these two functions were superimposed on the standardized time axis, suggesting a scalar property. In the session-by-session analysis, the mean peak time (an index of timing accuracy) of the muscimol group was lower than that of the control group in the probe sessions, but not in the shift sessions. In the trial-by-trial analysis, the mean start time and stop times (indices of timing accuracy) were lower than in the control group in the probe sessions. These findings suggest that the dorsal hippocampus is required for the formation of long-term duration memories within the range of interval timing.

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“…Given the intimate relationship between time and information in episodic memory, it is possible that the hippocampus would be sensitive to event duration at different time scales. In addition to the varying scales formed via neural ensembles (Howard et al, 2014), the hippocampus has been shown to be sensitive to time on the order of seconds (Barnett et al, 2014; Thavabalasingam et al, 2018) as well as on the order of minutes (Montchal et al, 2019); for an excellent review, see Lee et al [2020]]). Given that pattern separation processes have been detected within hippocampal circuitry (Gilbert & Kesner, 2006; Gilbert et al, 1998; Gilbert et al, 2001; Hunsaker & Kesner, 2013), that pattern separation processes are information agnostic (Huffman & Stark, 2014; Yassa & Stark, 2011), and hippocampal sensitivity to temporal information, we expect the hippocampus to be capable of discriminating between similar but different temporal properties within episodic memory.…”

Section: Introductionmentioning

confidence: 99%

The Medial Temporal Lobe Supports Mnemonic Discrimination For Event Duration

Muncy

Kirwan

2020

Preprint

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Time has an integral role in episodic memory and previous work has implicated the medial temporal lobe in both representing time and discriminating between similar information. Here we developed a novel paradigm to test mnemonic discrimination for temporal duration, as previous work has largely focused on order or maintaining information over time. Thirty-five healthy, young adults completed a continuous-recognition, temporal discrimination task in which participants were tasked with detecting a change in stimulus duration on the order of 0.5 seconds.Whole-brain high-resolution fMRI data were acquired. Behavioral results indicate that participants were successful at detecting whether or not the stimulus duration changed. Further, fMRI analyses revealed that the left entorhinal and perirhinal cortices were differentially involved in encoding and retrieval, respectively. These findings support the notion of the entorhinal cortex being involved in the encoding of temporal context information as well as the perirhinal cortex representing the conjunction of item and context during retrieval.then the duration of the second presentation was adjusted by 0.5s, where if the first presentation 131 had a duration of 1s then the second presentation had a duration of 1.5s, and vice versa; in this 132 way all stimuli (Target, Lure, Foil) were presented for either 1 or 1.5s but Lure trials either 133

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The hippocampus contributes to temporal duration memory in the context of event sequences: A cross-species perspective

Cited by 24 publications

References 256 publications

Chronic Neurobehavioral Impairments and Decreased Hippocampal Expression of Genes Important for Brain Glucose Utilization in a Mouse Model of Mild TBI

Chronic Neurobehavioral Impairments and Decreased Hippocampal Expression of Genes Important for Brain Glucose Utilization in a Mouse Model of Mild TBI

The dorsal hippocampus is required for the formation of long-term duration memories in rats

The Medial Temporal Lobe Supports Mnemonic Discrimination For Event Duration

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