Theta Oscillations Coincide with Sustained Hyperpolarization in CA3 Pyramidal Cells, Underlying Decreased Firing

Malézieux, Meryl; Kees, Ashley L.; Mulle, Christophe

doi:10.1016/j.celrep.2020.107868

Cited by 17 publications

(11 citation statements)

References 70 publications

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“…Similarly, in CA3 principal cells, activation of nAChRs by low concentration of nicotine enhances GABA release either directly ( Hajós et al, 2005 ) or indirectly, via NMDA receptors localized on GABAergic interneurons ( Mann and Mody, 2010 ; Wang et al, 2015 ). Furthermore, previous studies showed that brain states associated with high cholinergic activity and theta oscillations resulted in CA3 principal neuron inhibition via activation of interneurons ( Malezieux et al, 2020 ; Dannenberg et al, 2015 ). Thus, enhanced GABAergic tone may lead, as in CA1, to a reduced glutamate release from CA3 principal cells.…”

Section: Discussionmentioning

confidence: 98%

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Pimpinella

Mastrorilli

Giorgi

et al. 2021

eLife

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Acetylcholine (ACh), released in the hippocampus from fibers originating in the medial septum/diagonal band of Broca (MSDB) complex, is crucial for learning and memory. The CA2 region of the hippocampus has received increasing attention in the context of social memory. However, the contribution of ACh to this process remains unclear. Here, we show that in mice, ACh controls social memory. Specifically, MSDB cholinergic neurons inhibition impairs social novelty discrimination, meaning the propensity of a mouse to interact with a novel rather than a familiar conspecific. This effect is mimicked by a selective antagonist of nicotinic AChRs delivered in CA2. Ex vivo recordings from hippocampal slices provide insight into the underlying mechanism, as activation of nAChRs by nicotine increases the excitatory drive to CA2 principal cells via disinhibition. In line with this observation, optogenetic activation of cholinergic neurons in MSDB increases the firing of CA2 principal cells in vivo. These results point to nAChRs as essential players in social novelty discrimination by controlling inhibition in the CA2 region.

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Section: Discussionmentioning

confidence: 98%

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Pimpinella

Mastrorilli

Giorgi

et al. 2021

eLife

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“…Whole cell recordings in awake animals have opened a window to understanding the interplay between collective network activity and membrane potential (Vm) dynamics of hippocampal neurons which can reveal the nature and timing of synaptic inputs and subthreshold changes that are invisible to extracellular recordings. While recent efforts have examined the Vm of CA1 neurons around ripples (English et al, 2014;Hulse et al, 2016) and the Vm modulation by brain state across hippocampal subfields (Hulse et al, 2017;Malezieux et al, 2020), the subthreshold dynamics of CA3 pyramidal cells around ripples and the impact of cortical inputs on Vm behavior in CA3 remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples

Kajikawa

Hulse

Siapas

et al. 2021

Preprint

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Hippocampal ripples are transient population bursts that structure cortico-hippocampal communication and play a central role in memory processing. However, the mechanisms controlling ripple initiation in behaving animals remain poorly understood. Here we combine multisite extracellular and whole cell recordings in awake mice to contrast the brain state and ripple modulation of subthreshold dynamics across hippocampal subfields. We find that entorhinal input to DG exhibits UP and DOWN dynamics with ripples occurring exclusively in UP states. While elevated cortical input in UP states generates depolarization in DG and CA1, it produces persistent hyperpolarization in CA3 neurons. Furthermore, growing inhibition is evident in CA3 throughout the course of the ripple buildup, while DG and CA1 neurons exhibit depolarization transients 100 ms before and during ripples. These observations highlight the importance of CA3 inhibition for ripple generation, while pre-ripple responses indicate a long and orchestrated ripple initiation process in the awake state.

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“…However, it is not straightforward to relate the changes in calcium transient frequency that we observed to changes in AP patterns. Moreover, recent in vivo whole-cell recordings found that theta oscillations were associated with membrane potential hyperpolarization in most CA3 pyramidal neurons ( Malezieux et al, 2020 ), which could imply decreased average firing rates during running. However, theta periods included both resting and running periods and modulatory effects were quite heterogeneous across the CA3 population.…”

Section: Discussionmentioning

confidence: 99%

“…CA3 pyramidal neurons are special in forming an auto-associative recurrent network enabling memory encoding and pattern completion ( Rolls, 2007 ; Kesner and Rolls, 2015 ; Guzman et al, 2016 ; Knierim and Neunuebel, 2016 ). The functional properties of CA3 pyramidal neurons have been characterized largely with electrophysiology, using extracellular recordings ( Fox and Ranck, 1975 ; Csicsvari et al, 2000 ; Henze et al, 2002 ; Leutgeb et al, 2004 ; Frerking et al, 2005 ; Mizuseki et al, 2012 ; Oliva et al, 2016 ), in vivo intracellular and juxtacellular recordings ( Epsztein et al, 2011 ; Kowalski et al, 2016 ; Zucca et al, 2017 ; Diamantaki et al, 2018 ; Hunt et al, 2018 ; Malezieux et al, 2020 ), and whole-cell recordings in brain slices ( Jonas et al, 1993 ; Hemond et al, 2008 ; Hunt et al, 2018 ; Raus Balind et al, 2019 ). Pyramidal neurons in CA3 show properties distinct from CA1 ( Mizuseki et al, 2012 ; Oliva et al, 2016 ) but display heterogeneity within their population ( Hunt et al, 2018 ; Cembrowski and Spruston, 2019 ; Ding et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

In VivoCalcium Imaging of CA3 Pyramidal Neuron Populations in Adult Mouse Hippocampus

Schoenfeld

Carta

Rupprecht

et al. 2021

eNeuro

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Neuronal population activity in the hippocampal CA3 subfield is implicated in cognitive brain functions such as memory processing and spatial navigation. However, because of its deep location in the brain, the CA3 area has been difficult to target with modern calcium imaging approaches. Here, we achieved chronic two-photon calcium imaging of CA3 pyramidal neurons with the red fluorescent calcium indicator R-CaMP1.07 in anesthetized and awake mice. We characterize CA3 neuronal activity at both the single-cell and population level and assess its stability across multiple imaging days. During both anesthesia and wakefulness, nearly all CA3 pyramidal neurons displayed calcium transients. Most of the calcium transients were consistent with a high incidence of bursts of action potentials, based on calibration measurements using simultaneous juxtacellular recordings and calcium imaging. In awake mice, we found statedependent differences with striking large and prolonged calcium transients during locomotion.We estimate that trains of >30 action potentials over 3 s underlie these salient events. Their abundance in particular subsets of neurons was relatively stable across days. At the population level, we found that co-activity within the CA3 network was above chance level and that coactive neuron pairs maintained their correlated activity over days. Our results corroborate the notion of state-dependent spatiotemporal activity patterns in the recurrent network of CA3 and demonstrate that at least some features of population activity, namely co-activity of cell pairs and likelihood to engage in prolonged high activity, are maintained over days. Significance StatementIn vivo measurements of neuronal population activity may reveal how the mammalian hippocampus supports fundamental brain functions such as memory. So far, however, calcium imaging in deep hippocampal regions such as the CA3 subfield has been rarely achieved. Here, we utilize a red calcium indicator to measure CA3 pyramidal neuron activity in the mouse brain 5 during different states (anesthetized vs. awake [resting or running]) and across days. Most CA3 pyramidal neurons displayed calcium transients consistent with complex spike bursts. During running, salient large and prolonged calcium signals were prominent. Some features of neuronal activity remained relatively stable over days, e.g., co-activity in neuronal pairs. Our study further expands CA3 calcium imaging in behaving mice, fostering analysis of CA3 network activity.

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Theta Oscillations Coincide with Sustained Hyperpolarization in CA3 Pyramidal Cells, Underlying Decreased Firing

Cited by 17 publications

References 70 publications

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition

Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples

In VivoCalcium Imaging of CA3 Pyramidal Neuron Populations in Adult Mouse Hippocampus

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