Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit

Fuhrmann, Falko; Justus, Daniel; Sosulina, Liudmila; Kaneko, Hiroshi; Beutel, Tatjana; Friedrichs, Detlef; Schoch, Susanne; Schwarz, Martin K.; Fuhrmann, Martin; Remy, Stefan

doi:10.1016/j.neuron.2015.05.001

Cited by 306 publications

(380 citation statements)

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“…As for MS-DBB GABAergic neurons, these neurons have unique connectivity to GABAergic interneurons in the hippocampus and strongly fire phase-locked to theta, suggesting that they play an important role in theta generation (Petsche et al, 1962;Freund and Antal, 1988;Stewart and Fox, 1990;Hangya et al, 2009;Bender et al, 2015). Finally, recent in vivo evidence has shown that activation of glutamatergic neurons in the MS-DBB initiates both theta rhythms and locomotor activity in the head-restrained animal (Fuhrmann et al, 2015). Results from this study suggest that direct glutamatergic MS-DBB projections drive interneurons in the stratum oriens, which in turn influence CA1 pyramidal cell firing.…”

Section: Discussionsupporting

confidence: 50%

Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms

et al. 2016

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The medial septum and diagonal band of Broca (MS-DBB) has an essential role for theta rhythm generation in the hippocampus and is critical for learning and memory. The MS-DBB contains cholinergic, GABAergic, and recently described glutamatergic neurons, but their specific contribution to theta generation is poorly understood. Here, we examined the role of MS-DBB glutamatergic neurons in theta rhythm using optogenetic activation and electrophysiological recordings performed in in vitro preparations and in freely behaving mice. The experiments in slices suggest that MS-DBB glutamatergic neurons provide prominent excitatory inputs to a majority of local GABAergic and a minority of septal cholinergic neurons. In contrast, activation of MS-DBB glutamatergic fiber terminals in hippocampal slices elicited weak postsynaptic responses in hippocampal neurons. In the in vitro septo-hippocampal preparation, activation of MS-DBB glutamatergic neurons did increase the rhythmicity of hippocampal theta oscillations, whereas stimulation of septo-hippocampal glutamatergic fibers in the fornix did not have an effect. In freely behaving mice, activation of these neurons in the MS-DBB strongly synchronized hippocampal theta rhythms over a wide range of frequencies, whereas activation of their projections to the hippocampus through fornix stimulations had no effect on theta rhythms, suggesting that MS-DBB glutamatergic neurons played a role in theta generation through local modulation of septal neurons. Together, these results provide the first evidence that MS-DBB glutamatergic neurons modulate local septal circuits, which in turn contribute to theta rhythms in the hippocampus.

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Section: Discussionsupporting

confidence: 50%

Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms

et al. 2016

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“…Hippocampal neurons also play an important role in the onset of locomotion and exhibit locomotion velocity-dependent firing with theta oscillation (39). Although untested, glycogen-derived lactate might be a contributor to locomotion-dependent hippocampal firing.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

Matsui

Omuro

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

123

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Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresismass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxycinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.brain glycogen | lactate transport | ATP | endurance capacity | metabolomics G lucose derived from blood is the primary energy source for generating ATP in the brain, but an important energy reserve is brain glycogen synthesized from glucose in astrocytes (1). Astrocytic glycogen is broken down through glycogenolysis/glycolysis to produce lactate as a neuronal energy substrate transported by monocarboxylate transporters (MCTs) (2). Indeed, brain glycogen decreases during memory tasks (3) and in some physiologically exhaustive conditions such as sleep deprivation (4) and hypoglycemia (5). The genetic/pharmacologic inhibitions of glycogenolysis and/or lactate transport impair neuronal survival under severe hypoglycemia, as well as axon transmission and hippocampus-related memory formation (6-8). Therefore, astrocytic glycogen-derived lactate is a critical energy source for meeting brain energy demands for neuronal functions and/or survival.Although less than for exercising muscles, physical exercise activates brain neurons and increases brain energy demand (9). Blood glucose and lactate contribute to brain energetics during moderate or intense exercise (10, 11). Muscle glycogen is an important energy for maintaining muscle contraction during endurance ex...

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“…http://dx.doi.org/10.1101/211458 doi: bioRxiv preprint first posted online Oct. 30, 2017; 18,258, p = 0.0277) but nonphasers were more widely distributed (range, [0, 0.199 ( Figure 7B, S, gray) consistent with extensive speed modulation in space-related brain areas 288 (Fuhrmann et al, 2015;Kropff et al, 2015). Sorted matrixes of cell-level data confirmed this 289 pattern and showed an inverse relationship between spatial and speed contributions 290…”

mentioning

confidence: 81%

Spatial Theta Cells in Competitive Burst Synchronization Networks: Reference Frames from Phase Codes

Monaco

Blair²,

Zhang

2017

Preprint

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1Spatial cells of the hippocampal formation are embedded in networks of theta cells. The septal 2 theta rhythm (6-10 Hz) organizes the spatial activity of place and grid cells in time, but it remains 3 unclear how spatial reference points organize the temporal activity of theta cells in space. We 4 study spatial theta cells in simulations and single-unit recordings from exploring rats to ask 5 whether temporal phase codes may anchor spatial representations to the outside world. We 6 theorize that an experience-independent mechanism for temporal coding may combine with 7 burst synchronization to continuously calibrate self-motion to allocentric reference frames.

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Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit

Cited by 306 publications

References 70 publications

Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms

Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

Spatial Theta Cells in Competitive Burst Synchronization Networks: Reference Frames from Phase Codes

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