Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex

Filippo, Roberto De; Rost, Benjamin R.; Stumpf, Alexander; Cooper, Claire; Tukker, John J.; Harms, Christoph; Beed, Prateep; Schmitz, Dietmar

doi:10.7554/elife.66960

Cited by 26 publications

(25 citation statements)

References 113 publications

(105 reference statements)

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“…It seems highly likely that these interneuron classes also have distinct behaviours and roles in the modulation of cortical activity by psychedelics. For example, earlier this year it was reported that a subset of SST entorhinal cortex neurons is strongly activated by their 5-HT2ARs, leading to a profound suppression of population activity by serotonin and serotonin-releasing drugs in vitro and in anaesthetised mice (de Filippo et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

Dearnley

Dervinis

Shaw

et al. 2021

Preprint

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How psychedelic drugs change the activity of cortical neuronal populations and whether such changes are specific to transition into the psychedelic brain state or shared with other brain state transitions is not well understood. Here, we used Neuropixels probes to record from large populations of neurons in prefrontal cortex of mice given the psychedelic drug TCB-2. Drug ingestion significantly stretched the distribution of log firing rates of the population of recorded neurons. This phenomenon was previously observed across transitions between sleep and wakefulness, which suggested that stretching of the log-rate distribution can be triggered by different kinds of brain state transitions and prompted us to examine it in more detail. We found that modulation of the width of the log-rate distribution of a neuronal population occurred in multiple areas of the cortex and in the hippocampus even in awake drug-free mice, driven by intrinsic fluctuations in their arousal level. Arousal, however, did not explain the stretching of the log-rate distribution by TCB-2. In both psychedelic and naturally occurring brain state transitions, the stretching or squeezing of the log-rate distribution of an entire neuronal population reflected concomitant changes in two subpopulations, with one subpopulation undergoing a downregulation and often also stretching of its neurons' log-rate distribution, while the other subpopulation undergoes upregulation and often also a squeeze of its log-rate distribution. In both subpopulations, the stretching and squeezing were a signature of a greater relative impact of the brain state transition on the rates of the slow-firing neurons. These findings reveal a generic pattern of reorganisation of neuronal firing rates by different kinds of brain state transitions.

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Section: Discussionmentioning

confidence: 99%

Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

Dearnley

Dervinis

Shaw

et al. 2021

Preprint

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“…The REBUS model proposes a unifying account of how serotonergic psychedelic compounds affect conscious experience [32]. Serotonergic psychedelics are a specific class of psychoactive compounds including but not limited to lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), that principally act upon cortical serotonin 2A receptors [54][55][56][57][58][59][60][61][62][63][64] to achieve their profound psychological effects [32,65,66] and therapeutic potential [67][68][69][70][71][72]. Moving forward, we use the term psychedelics to refer to these serotonergic psychedelics.…”

Section: Relaxed Beliefs Under Psychedelics (Rebus)mentioning

confidence: 99%

Prefrontal contributions to the stability and variability of thought and conscious experience

Zamani

Carhart‐Harris

Christoff

2021

Neuropsychopharmacol.

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The human prefrontal cortex is a structurally and functionally heterogenous brain region, including multiple subregions that have been linked to different large-scale brain networks. It contributes to a broad range of mental phenomena, from goal-directed thought and executive functions to mind-wandering and psychedelic experience. Here we review what is known about the functions of different prefrontal subregions and their affiliations with large-scale brain networks to examine how they may differentially contribute to the diversity of mental phenomena associated with prefrontal function. An important dimension that distinguishes across different kinds of conscious experience is the stability or variability of mental states across time. This dimension is a central feature of two recently introduced theoretical frameworks—the dynamic framework of thought (DFT) and the relaxed beliefs under psychedelics (REBUS) model—that treat neurocognitive dynamics as central to understanding and distinguishing between different mental phenomena. Here, we bring these two frameworks together to provide a synthesis of how prefrontal subregions may differentially contribute to the stability and variability of thought and conscious experience. We close by considering future directions for this work.

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“…Fast-firing interneurons also provide the sole synaptic communication path between stellate cells, which lack recurrent excitatory connections ( Couey et al, 2013 ; Pastoll et al, 2013 ; but see Fuchs et al, 2016 ). In contrast, a subset of low threshold-spiking interneurons have been shown to suppress network oscillations in mEC ( de Filippo et al, 2021 ). Further, in behaving animals, inhibition from layer 2/3 parvalbumin-positive (Pvalb + ) and somatostatin-positive (Sst + ) interneurons have separate roles in setting the spatial tuning and firing rates of layer 2 grid cells ( Miao et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Kinetics and Connectivity Properties of Parvalbumin- and Somatostatin-Positive Inhibition in Layer 2/3 Medial Entorhinal Cortex

Fernandez

Via

Canavier

et al. 2022

eNeuro

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Parvalbumin (Pvalb + )-and somatostatin (Sst + )-positive cells are the two largest subgroups of inhibitory interneurons. Studies in visual cortex indicate that synaptic connections between Pvalb + cells are common while connections between Sst + interneurons have not been observed. The inhibitory connectivity and kinetics of these two interneuron subpopulations, however, have not been characterized in medial entorhinal cortex (mEC). Using fluorescence-guided paired recordings in mouse brain slices from interneurons and excitatory cells in layer 2/3 mEC, we found that, unlike neocortical measures, Sst + cells inhibit each other, albeit with a lower probability than Pvalb + cells (18% versus 36% for unidirectional connections). Gap junction connections were also more frequent between Pvalb + cells than between Sst + cells. Pvalb + cells inhibited each other with larger conductances, smaller decay time constants and shorter delays. Similarly, synaptic connections between Pvalb + and excitatory cells were more likely and expressed faster decay times and shorter delays than those between Sst + and excitatory cells. Inhibitory cells exhibited smaller synaptic decay time constants between interneurons than on their excitatory targets. Inhibition between interneurons also depressed faster, and to a greater extent. Finally, inhibition onto layer 2 pyramidal and stellate cells originating from Pvalb + interneurons were very similar, with no significant differences in connection likelihood, inhibitory amplitude, and decay time. A model of short-term depression fitted to the data indicates that recovery time constants for refilling the available pool are in the range of 50-150 ms and that the fraction of the available pool released on each spike is in the range 0.2-0.5. SignificanceTwo large and distinct classes of interneurons in medial entorhinal cortex (mEC) include parvalbumin (Pvalb + )-and somatostatin (Sst + )-positive cells. Previous work has demonstrated unique functions with regards to spatial tuning and network oscillations for these two interneuron populations. Potential differences in kinetics of inhibition and likelihood of connection from these two interneuron groups, however, have not been quantified. Here, using fluorescence to guide intracellular recordings, we quantified the synaptic connections from both types of interneurons. We indicate that Sst + and Pvalb + express different synaptic kineticsare target-cell specific. In contrast to neocortical measures, we find substantial connections between Sst + interneurons.

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Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex

Cited by 26 publications

References 113 publications

Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

Prefrontal contributions to the stability and variability of thought and conscious experience

Kinetics and Connectivity Properties of Parvalbumin- and Somatostatin-Positive Inhibition in Layer 2/3 Medial Entorhinal Cortex

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