scholarly journals Early hippocampal hyperexcitability followed by disinhibition in a mouse model of Dravet syndrome

2019 ◽  
Author(s):  
Yael Almog ◽  
Marina Brusel ◽  
Karen Anderson ◽  
Moran Rubinstein
Keyword(s):  
Pyramidal Neurons ◽  
Febrile Seizures ◽  
Cell Types ◽  
Dravet Syndrome ◽  
Inhibitory Neurons ◽  
Temporary Increase ◽  
Ca1 Pyramidal Neurons ◽  
Spontaneous Seizures ◽  
Hippocampal Ca1 ◽  
Firing Properties

AbstractDravet syndrome (Dravet) epilepsy begins with febrile seizures followed by worsening to refractory seizures, with some improvement and stabilization toward adolescence. The neuronal basis of Dravet is debatable, with evidence favoring reduced inhibition or enhanced excitation. Focusing on the firing properties of hippocampal CA1 pyramidal neurons and oriens-lacunosum moleculare (O-LM) interneurons, we provide a comprehensive analysis of the activity of both cell types through the febrile, worsening and stabilization stages. Our data indicate a temporary increase in the excitability of CA1 pyramidal neurons during the febrile stage, which is fully reversed by the onset of spontaneous seizures. In contrast, reduced function of O-LM interneurons persisted from the febrile through the stabilization stages, with the greatest impairment of excitability occurring during the worsening stage. Thus, both excitatory and inhibitory neurons contribute to Dravet, indicating complex and reciprocal pathophysiological neuronal changes during the different stages of the disease.Graphical abstract

scholarly journals 3P221 The endocrine disrupter Bisphenol-A acutely induces morphologica changes in rat hippocampal CA1 pyramidal neurons

2004 ◽  
Vol 44 (supplement) ◽  
pp. S245
Author(s):  
N Tanabe ◽  
Y Komatsuzaki ◽  
T Tsurugizawa ◽  
K Mitsuhashi ◽  
Y Ooishi ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Pyramidal Neurons ◽  
Endocrine Disrupter ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1

scholarly journals Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Nutrients ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 749 ◽  
Author(s):  
Stine Hansen ◽  
Jane Jørgensen ◽  
Jens Nyengaard ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg
Keyword(s):  
Synaptic Plasticity ◽  
Vitamin C ◽  
Guinea Pig ◽  
Early Life ◽  
Pyramidal Neurons ◽  
Pig Model ◽  
Vitamin C Deficiency ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Guinea Pig Model

Modulation of the Ca2+-Activated K+ Current sI AHP by aPhosphatase-Kinase Balance Under Basal Conditions inRat CA1 Pyramidal Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 3252-3256 ◽  
Author(s):  
Paola Pedarzani ◽  
Michael Krause ◽  
Trude Haug ◽  
Johan F. Storm ◽  
Walter Stühmer
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Phosphodiesterase Inhibitors ◽  
Gradual Decrease ◽  
Patch Clamp Technique ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Type Iv ◽  
Whole Cell Patch Clamp ◽  
Firing Properties

Pedarzani, Paola, Michael Krause, Trude Haug, Johan F. Storm, and Walter Stühmer. Modulation of the Ca2+-activated K+ current s I AHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons. J. Neurophysiol. 79: 3252–3256, 1998. The slow Ca2+-activated K+ current, s I AHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of s I AHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating s I AHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of s I AHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-γ-S, caused a gradual decrease in the s I AHP amplitude, supporting a role of protein phosphorylation in the basal modulation of s I AHP. When the protein kinase A (PKA) inhibitor adenosine-3′,5′-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the s I AHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the s I AHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22,536) and adenosine 3′,5′-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20–1724 and rolipram) led to an increase or a decrease in the s I AHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of s I AHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism

2002 ◽  
Vol 88 (1) ◽  
pp. 107-116 ◽  
Author(s):  
David R. Ireland ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Subtypes ◽  
Ca1 Pyramidal Neurons ◽  
Group I ◽  
Hippocampal Ca1 ◽  
Group I Mglurs ◽  
Induced Changes

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP3)-activated Ca2+ stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP3-independent transduction pathway.

scholarly journals Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit

2022 ◽  
Author(s):  
Olesia M Bilash ◽  
Spyridon Chavlis ◽  
Panayiota Poirazi ◽  
Jayeeta Basu
Keyword(s):  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Environmental Cues ◽  
Memory Processing ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spikes ◽  
Hippocampal Area ◽  
Insight Into

The lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.

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