Dentate gyrus mossy cells exhibit sparse coding via adaptive spike threshold dynamics

Trinh, Anh‐Tuan; Girardi‐Schappo, Mauricio; Béı̈que, Jean-Claude; Longtin, André; Maler, Leonard

doi:10.1101/2022.03.07.483263

Cited by 2 publications

(1 citation statement)

References 62 publications

(119 reference statements)

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“…For example, the mechanism of the adaptation of excitability appears to be a key factor in the transition between spike and burst patterns [ 34 , 35 ]. Typically, spike adaptation corresponds to the capability of neurons to reduce their spike frequency due to recent sub and over-threshold neuronal activities [ 36 , 37 , 38 ]. It is also known that potassium and calcium currents develop a role in neuronal adaptation mechanisms [ 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

The Roles of Potassium and Calcium Currents in the Bistable Firing Transition

Borges,

Protachevicz,

Souza

et al. 2023

Brain Sciences

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Healthy brains display a wide range of firing patterns, from synchronized oscillations during slow-wave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking (RS) cells with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings (gsyn) and external current inputs (I). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to the bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold (IL) and low-threshold (IT) ion channels play a role in increasing and decreasing the parameter conditions (gsyn and I) in which bistable dynamics occur, respectively. For high values of IL conductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductance IT increases, higher coupling and lower I are necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states.

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Section: Introductionmentioning

confidence: 99%

The Roles of Potassium and Calcium Currents in the Bistable Firing Transition

Borges,

Protachevicz,

Souza

et al. 2023

Brain Sciences

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Dopamine D2 receptors in mossy cells reduce excitatory transmission and are essential for hippocampal function

Gulfo

Lebowitz

Ramos

et al. 2023

Preprint

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Hilar mossy cells (MCs) are principal excitatory neurons of the dentate gyrus (DG) that play critical roles in hippocampal function and have been implicated in brain disorders such as anxiety and epilepsy. However, the mechanisms by which MCs contribute to DG function and disease are poorly understood. Expression from the dopamine D2 receptor (D2R) gene (Drd2) promoter is a defining feature of MCs, and previous work indicates a key role for dopaminergic signaling in the DG. Additionally, the involvement of D2R signaling in cognition and neuropsychiatric conditions is well-known. Surprisingly, though, the function of MC D2Rs remain largely unexplored. In this study, we show that selective and conditional removal of Drd2 from MCs of adult mice impaired spatial memory, promoted anxiety-like behavior and was proconvulsant. To determine the subcellular expression of D2Rs in MCs, we used a D2R knockin mouse which revealed that D2Rs are enriched in the inner molecular layer of the DG, where MCs establish synaptic contacts with granule cells. D2R activation by exogenous and endogenous dopamine reduced MC to dentate granule cells (GC) synaptic transmission, most likely by a presynaptic mechanism. In contrast, removing Drd2 from MCs had no significant impact on MC excitatory inputs and passive and active properties. Our findings support that MC D2Rs are essential for proper DG function by reducing MC excitatory drive onto GCs. Lastly, impairment of MC D2R signaling could promote anxiety and epilepsy, therefore highlighting a potential therapeutic target.

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Dentate gyrus mossy cells exhibit sparse coding via adaptive spike threshold dynamics

Cited by 2 publications

References 62 publications

The Roles of Potassium and Calcium Currents in the Bistable Firing Transition

The Roles of Potassium and Calcium Currents in the Bistable Firing Transition

Dopamine D2 receptors in mossy cells reduce excitatory transmission and are essential for hippocampal function

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