scholarly journals Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Vincent Robert ◽  
Ludivine Therreau ◽  
Vivien Chevaleyre ◽  
Eude Lepicard ◽  
Cécile Viollet ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Social Memory ◽  
Memory Encoding ◽  
Action Potential Firing ◽  
Local Circuit ◽  
Supramammillary Nucleus ◽  
Hypothalamic Control ◽  
Potential Firing ◽  
Cholinergic Tone ◽  
Hippocampal Area

The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. Using mice, we found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). Parvalbumin-expressing basket cells were largely responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulated CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.

scholarly journals Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

2020 ◽  
Author(s):  
Vincent Robert ◽  
Ludivine Therreau ◽  
Arthur J.Y. Huang ◽  
Roman Boehringer ◽  
Denis Polygalov ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Social Memory ◽  
Memory Encoding ◽  
Action Potential Firing ◽  
Local Circuit ◽  
Supramammillary Nucleus ◽  
Hypothalamic Control ◽  
Potential Firing ◽  
Cholinergic Tone ◽  
Hippocampal Area

AbstractThe hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. We found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). We found that parvalbumin-expressing basket cells as responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulates CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.

scholarly journals Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex

2013 ◽  
Vol 110 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Jonathan Dilgen ◽  
Hugo A. Tejeda ◽  
Patricio O'Donnell
Keyword(s):  
Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Intracellular Recordings ◽  
Action Potential Firing ◽  
Gaba A ◽  
Potential Firing ◽  
Feedforward Inhibition

Although interactions between the amygdala and prefrontal cortex (PFC) are critical for emotional guidance of behavior, the manner in which amygdala affects PFC function is not clear. Whereas basolateral amygdala (BLA) output neurons exhibit many characteristics associated with excitatory neurotransmission, BLA stimulation typically inhibits PFC cell firing. This apparent discrepancy could be explained if local PFC inhibitory interneurons were activated by BLA inputs. Here, we used in vivo juxtacellular and intracellular recordings in anesthetized rats to investigate whether BLA inputs evoke feedforward inhibition in the PFC. Juxtacellular recordings revealed that BLA stimulation evoked action potentials in PFC interneurons and silenced most pyramidal neurons. Intracellular recordings from PFC pyramidal neurons showed depolarizing postsynaptic potentials, with multiple components evoked by BLA stimulation. These responses exhibited a relatively negative reversal potential (Erev), suggesting the contribution of a chloride component. Intracellular administration or pressure ejection of the GABA-A antagonist picrotoxin resulted in action-potential firing during the BLA-evoked response, which had a more depolarized Erev. These results suggest that BLA stimulation engages a powerful inhibitory mechanism within the PFC mediated by local circuit interneurons.

Neuromodulation by a Cytokine: Interferon-β Differentially Augments Neocortical Neuronal Activity and Excitability

2005 ◽  
Vol 93 (2) ◽  
pp. 843-852 ◽  
Author(s):  
Gergana Hadjilambreva ◽  
Eilhard Mix ◽  
Arndt Rolfs ◽  
Jana Müller ◽  
Ulf Strauss
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Membrane Resistance ◽  
Interferon Β ◽  
Action Potential Firing ◽  
Somatosensory Neurons ◽  
Potential Firing ◽  
Intracellular Process ◽  
Neuronal Functions

The immunomodulatory cytokine interferon-β (IFN-β) is used in the treatment of autoimmune diseases such as multiple sclerosis. However, the effect of IFN-β on neuronal functions is currently unknown. Intracellular recordings were conducted on somatosensory neurons of neocortical layers 2/3 and 5 exposed to IFN-β. The excitability of neurons was increased by IFN-β (10–10,000 U/ml) in two kinetically distinct, putatively independent manners. First IFN-β reversibly influenced the subthreshold membrane response by raising the membrane resistance RM 2.5-fold and the membrane time constant τ 1.7-fold dose-dependently. The effect required permanent exposure to IFN-β and was reduced in magnitude if the extracellular K+ was lowered. However, the membrane response to IFN-β in the subthreshold range was prevented by ZD7288 (a specific blocker of Ih) but not by Ni2+, carbachol, or bicuculline, pointing to a dependence on an intact Ih. Second, IFN-β enhanced the rate of action potential firing. This effect was observed to develop for >1 h when the cell was exposed to IFN-β for 5 min or >5 min and showed no reversibility (≤210 min). Current-discharge ( F-I) curves revealed a shift (prevented by bicuculline) as well as an increase in slope (prevented by carbachol and Ni2+). Layer specificity was not observed with any of the described effects. In conclusion, IFN-β influences the neuronal excitability in neocortical pyramidal neurons in vitro, especially under conditions of slightly increased extracellular K+. Our blocker experiments indicate that changes in various ionic conductances with different voltage dependencies cause different IFN-β influences on sub- and suprathreshold behavior, suggesting a more general intracellular process induced by IFN-β.

scholarly journals Interneuron dysfunction in a new knock-in mouse model of SCN1A GEFS+

2019 ◽  
Author(s):  
Antara Das ◽  
Bingyao Zhu ◽  
Yunyao Xie ◽  
Lisha Zeng ◽  
An T. Pham ◽  
...  
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Inhibitory Interneurons ◽  
Wild Type ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Acute Hippocampal Slices ◽  
Firing Properties ◽  
Genetic Epilepsies

AbstractAdvances in genome sequencing have identified over 1300 mutations in the SCN1A sodium channel gene that result in genetic epilepsies. However, how individual mutations within SCN1A produce seizures remains elusive for most mutations. Previous work from our lab has shown that the K1270T (KT) mutation, which is linked to GEFS+ (Genetic Epilepsy with Febrile Seizure plus) in humans, causes reduced firing of GABAergic neurons in a Drosophila knock-in model. To examine the effect of this mutation in mammals, we introduced the equivalent KT mutation into the mouse Scn1a (Scn1aKT) gene using CRISPR/Cas9. Mouse lines carrying this mutation were examined in two widely used genetic backgrounds, C57BL/6NJ and 129×1/SvJ. In both backgrounds, homozygous mutants had spontaneous seizures and died by postnatal day 23. There was no difference in the lifespan of mice heterozygous for the mutation in either background when compared to wild-type littermates up to 6 months. Heterozygous mutants had heat-induced seizures at ~42 deg. Celsius, a temperature that did not induce seizures in wild-type littermates. In acute hippocampal slices, current-clamp recordings revealed a significant depolarized shift in action potential threshold and reduced action potential amplitude in parvalbumin-expressing inhibitory interneurons in Scn1aKT/+ mice. There was no change in the firing properties of excitatory CA1 pyramidal neurons. Our results indicate that Scn1aKT/+ mice develop seizures, and impaired action potential firing of inhibitory interneurons in Scn1aKT/+ mice may produce hyperexcitability in the hippocampus.

scholarly journals Dendritic position is a major determinant of presynaptic strength

2012 ◽  
Vol 197 (2) ◽  
pp. 327-337 ◽  
Author(s):  
Arthur P.H. de Jong ◽  
Sabine K. Schmitz ◽  
Ruud F.G. Toonen ◽  
Matthijs Verhage
Keyword(s):  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Cell Types ◽  
Synaptic Coupling ◽  
Action Potential Firing ◽  
Vesicle Release ◽  
Postsynaptic Receptors ◽  
Potential Firing ◽  
Mixed Networks ◽  
Different Cell Types

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.

scholarly journals Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice

2021 ◽  
Author(s):  
Nigel C. Dao ◽  
Dakota F. Brockway ◽  
Malini Suresh Nair ◽  
Avery R. Sicher ◽  
Nicole A. Crowley
Keyword(s):  
Binge Drinking ◽  
Pyramidal Neurons ◽  
Gaba Release ◽  
Depression And Anxiety ◽  
Action Potential Firing ◽  
Inhibitory Transmission ◽  
Reward Seeking ◽  
Potential Firing ◽  
Somatostatin Neurons ◽  
Drinking In The Dark

AbstractSomatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.

scholarly journals β3-Adrenergic receptor-dependent modulation of the medium afterhyperpolarization in rat hippocampal CA1 pyramidal neurons

2019 ◽  
Vol 121 (3) ◽  
pp. 773-784 ◽  
Author(s):  
Timothy W. Church ◽  
Jon T. Brown ◽  
Neil V. Marrion
Keyword(s):  
Action Potential ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Intracellular Camp ◽  
Action Potential Firing ◽  
Hippocampal Pyramidal Neurons ◽  
Potential Firing ◽  
H Channels

Action potential firing in hippocampal pyramidal neurons is regulated by generation of an afterhyperpolarization (AHP). Three phases of AHP are recognized, with the fast AHP regulating action potential firing at the onset of a burst and the medium and slow AHPs supressing action potential firing over hundreds of milliseconds and seconds, respectively. Activation of β-adrenergic receptors suppresses the slow AHP by a protein kinase A-dependent pathway. However, little is known regarding modulation of the medium AHP. Application of the selective β-adrenergic receptor agonist isoproterenol suppressed both the medium and slow AHPs evoked in rat CA1 hippocampal pyramidal neurons recorded from slices maintained in organotypic culture. Suppression of the slow AHP was mimicked by intracellular application of cAMP, with the suppression of the medium AHP by isoproterenol still being evident in cAMP-dialyzed cells. Suppression of both the medium and slow AHPs was antagonized by the β-adrenergic receptor antagonist propranolol. The effect of isoproterenol to suppress the medium AHP was mimicked by two β3-adrenergic receptor agonists, BRL37344 and SR58611A. The medium AHP was mediated by activation of small-conductance calcium-activated K+ channels and deactivation of H channels at the resting membrane potential. Suppression of the medium AHP by isoproterenol was reduced by pretreating cells with the H-channel blocker ZD7288. These data suggest that activation of β3-adrenergic receptors inhibits H channels, which suppresses the medium AHP in CA1 hippocampal neurons by utilizing a pathway that is independent of a rise in intracellular cAMP. This finding highlights a potential new target in modulating H-channel activity and thereby neuronal excitability. NEW & NOTEWORTHY The noradrenergic input into the hippocampus is involved in modulating long-term synaptic plasticity and is implicated in learning and memory. We demonstrate that activation of functional β3-adrenergic receptors suppresses the medium afterhyperpolarization in hippocampal pyramidal neurons. This finding provides an additional mechanism to increase action potential firing frequency, where neuronal excitability is likely to be crucial in cognition and memory.

scholarly journals The mechanisms shaping CA2 pyramidal neuron action potential bursting induced by muscarinic acetylcholine receptor activation

2020 ◽  
Vol 152 (4) ◽  
Author(s):  
Vincent Robert ◽  
Ludivine Therreau ◽  
M. Felicia Davatolhagh ◽  
F. Javier Bernardo-Garcia ◽  
Katie N. Clements ◽  
...  
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Membrane Resistance ◽  
Receptor Activation ◽  
Resting Membrane Potential ◽  
Intrinsic Properties ◽  
Action Potential Firing ◽  
Cholinergic Tone ◽  
Induced Changes

Recent studies have revealed that hippocampal area CA2 plays an important role in hippocampal network function. Disruption of this region has been implicated in neuropsychiatric disorders. It is well appreciated that cholinergic input to the hippocampus plays an important role in learning and memory. While the effect of elevated cholinergic tone has been well studied in areas CA1 and CA3, it remains unclear how changes in cholinergic tone impact synaptic transmission and the intrinsic properties of neurons in area CA2. In this study, we applied the cholinergic agonist carbachol and performed on-cell, whole-cell, and extracellular recordings in area CA2. We observed that under conditions of high cholinergic tone, CA2 pyramidal neurons depolarized and rhythmically fired bursts of action potentials. This depolarization depended on the activation of M1 and M3 cholinergic receptors. Furthermore, we examined how the intrinsic properties and action-potential firing were altered in CA2 pyramidal neurons treated with 10 µM carbachol. While this intrinsic burst firing persisted in the absence of synaptic transmission, bursts were shaped by synaptic inputs in the intact network. We found that both excitatory and inhibitory synaptic transmission were reduced upon carbachol treatment. Finally, we examined the contribution of different channels to the cholinergic-induced changes in neuronal properties. We found that a conductance from Kv7 channels partially contributed to carbachol-induced changes in resting membrane potential and membrane resistance. We also found that D-type potassium currents contributed to controlling several properties of the bursts, including firing rate and burst kinetics. Furthermore, we determined that T-type calcium channels and small conductance calcium-activated potassium channels play a role in regulating bursting activity.

scholarly journals Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

2018 ◽  
Vol 115 (28) ◽  
pp. 7434-7439 ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Kirill Volynski ◽  
Katalin Tóth
Keyword(s):  
Action Potential ◽  
Granule Cell ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Mossy Fibers ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Ca3 Pyramidal Neurons ◽  
Calbindin D

Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays constant during action potential trains and that accumulated residual Ca2+ is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+ dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+ buffers calbindin-D28K and calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+ channels and release sensors and the relatively slow Ca2+ extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.

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