scholarly journals Somatostatin and parvalbumin inhibitory synapses onto hippocampal pyramidal neurons are regulated by distinct mechanisms

2018 ◽  
Vol 115 (3) ◽  
pp. 589-594 ◽  
Author(s):  
Meryl E. Horn ◽  
Roger A. Nicoll
Keyword(s):  
Calcium Channels ◽  
Brain Function ◽  
Pyramidal Neurons ◽  
Neuronal Firing ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Hippocampal Pyramidal Neurons ◽  
Excitatory Neurons ◽  
Glutamatergic Signaling ◽  
Different Populations

Excitation–inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated by neuronal firing, signaling through L-type calcium channels. Synapses from somatostatin-expressing interneurons are regulated by NMDA receptors, signaling through R-type calcium channels. Thus, excitatory neurons can cell-autonomously regulate their inhibition onto different subcellular compartments through their input (glutamatergic signaling) and their output (firing). Separately, while somatostatin and parvalbumin synapses onto excitatory neurons are both dependent on a common set of postsynaptic proteins, including gephyrin, collybistin, and neuroligin-2, decreasing neuroligin-3 expression selectively decreases inhibition from somatostatin interneurons, and overexpression of neuroligin-3 selectively enhances somatostatin inhibition. These results provide evidence that excitatory neurons can selectively regulate two distinct sets of inhibitory synapses.

scholarly journals Somatic Colocalization of Rat SK1 and D class (Cav 1.2) L-type Calcium Channels in Rat CA1 Hippocampal Pyramidal Neurons

2001 ◽  
Vol 21 (20) ◽  
pp. RC175-RC175 ◽  
Author(s):  
Sarah E. H. Bowden ◽  
Stephanie Fletcher ◽  
David J. Loane ◽  
Neil V. Marrion
Keyword(s):  
Calcium Channels ◽  
Pyramidal Neurons ◽  
Hippocampal Pyramidal Neurons

Mutual Inhibition with Few Inhibitory Cells via Nonlinear Inhibitory Synaptic Interaction

2019 ◽  
Vol 31 (11) ◽  
pp. 2252-2265
Author(s):  
Felix Weissenberger ◽  
Marcelo Matheus Gauy ◽  
Xun Zou ◽  
Angelika Steger
Keyword(s):  
Neural Network ◽  
Nonlinear Interaction ◽  
Network Models ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Synaptic Connections ◽  
Mutual Inhibition ◽  
Neural Network Models ◽  
Excitatory Neurons ◽  
Inhibitory Population

In computational neural network models, neurons are usually allowed to excite some and inhibit other neurons, depending on the weight of their synaptic connections. The traditional way to transform such networks into networks that obey Dale's law (i.e., a neuron can either excite or inhibit) is to accompany each excitatory neuron with an inhibitory one through which inhibitory signals are mediated. However, this requires an equal number of excitatory and inhibitory neurons, whereas a realistic number of inhibitory neurons is much smaller. In this letter, we propose a model of nonlinear interaction of inhibitory synapses on dendritic compartments of excitatory neurons that allows the excitatory neurons to mediate inhibitory signals through a subset of the inhibitory population. With this construction, the number of required inhibitory neurons can be reduced tremendously.

scholarly journals Modeling unitary fields and the single-neuron contribution to local field potentials in the hippocampus

2019 ◽  
Author(s):  
Maria Teleńczuk ◽  
Bartosz Teleńczuk ◽  
Alain Destexhe
Keyword(s):  
Local Field ◽  
Computational Models ◽  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Simple Method ◽  
Hippocampal Pyramidal Neurons

AbstractSynaptic currents represent a major contribution to the local field potential (LFP) in brain tissue, but the respective contribution of excitatory and inhibitory synapses is not known. Here, we provide estimates of this contribution by using computational models of hippocampal pyramidal neurons, constrained by in vitro recordings. We focus on the unitary LFP (uLFP) generated by single neurons in the CA3 region of the hippocampus. We first reproduce experimental results for hippocampal basket cells, and in particular how inhibitory uLFP are distributed within hippocampal layers. Next, we calculate the uLFP generated by pyramidal neurons, using morphologically-reconstructed CA3 pyramidal cells. The model shows that the excitatory uLFP is of small amplitude, smaller than inhibitory uLFPs. Indeed, when the two are simulated together, inhibitory uLFPs mask excitatory uLFPs, which might create the illusion that the inhibitory field is generated by pyramidal cells. These results provide an explanation for the observation that excitatory and inhibitory uLFPs are of the same polarity, in vivo and in vitro. These results also show that somatic inhibitory currents are large contributors of the LFP, which is important information to interpret this signal. Finally, the results of our model might form the basis of a simple method to compute the LFP, which could be applied to point neurons for each cell type, thus providing a simple biologically-grounded method to calculate LFPs from neural networks.

scholarly journals A kernel-based method to calculate local field potentials from networks of spiking neurons

2020 ◽  
Author(s):  
Bartosz Telenczuk ◽  
Maria Telenczuk ◽  
Alain Destexhe
Keyword(s):  
Local Field ◽  
Pyramidal Neurons ◽  
Field Potential ◽  
Point Of View ◽  
Spiking Neurons ◽  
Inhibitory Neurons ◽  
List Type ◽  
Synaptic Currents ◽  
Hippocampal Pyramidal Neurons ◽  
Low Pass

AbstractBackgroundThe local field potential (LFP) is usually calculated from current sources arising from transmembrane currents, in particular in asymmetric cellular morphologies such as pyramidal neurons.New methodHere, we adopt a different point of view and relate the spiking of neurons to the LFP through efferent synaptic connections and provide a method to calculate LFPs.ResultsWe show that the so-called unitary LFPs (uLFP) provide the key to such a calculation. We show experimental measurements and simulations of uLFPs in neocortex and hippocampus, for both excitatory and inhibitory neurons. We fit a “kernel” function to measurements of uLFPs, and we estimate its spatial and temporal spread by using simulations of morphologically detailed reconstructions of hippocampal pyramidal neurons. Assuming that LFPs are the sum of uLFPs generated by every neuron in the network, the LFP generated by excitatory and inhibitory neurons can be calculated by convolving the trains of action potentials with the kernels estimated from uLFPs. This provides a method to calculate the LFP from networks of spiking neurons, even for point neurons for which the LFP is not easily defined. We show examples of LFPs calculated from networks of point neurons and compare to the LFP calculated from synaptic currents.ConclusionsThe kernel-based method provides a practical way to calculate LFPs from networks of point neurons.HighlightsWe provide a method to estimate the LFP from spiking neuronsThis method is based on kernels, estimated from experimental dataWe show applications of this method to calculate the LFP from networks of spiking neuronsWe show that the kernel-based method is a low-pass filtered version of the LFP calculated from synaptic currents

scholarly journals P38 Regulates Kainic Acid-Induced Seizure and Neuronal Firing via Kv4.2 Phosphorylation

2020 ◽  
Vol 21 (16) ◽  
pp. 5921
Author(s):  
Jia-hua Hu ◽  
Cole Malloy ◽  
Dax A. Hoffman
Keyword(s):  
Kainic Acid ◽  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Neuronal Firing ◽  
Dependent Manner ◽  
Membrane Excitability ◽  
Hippocampal Pyramidal Neurons ◽  
K Current

The subthreshold, transient A-type K+ current is a vital regulator of the excitability of neurons throughout the brain. In mammalian hippocampal pyramidal neurons, this current is carried primarily by ion channels comprising Kv4.2 α-subunits. These channels occupy the somatodendritic domains of these principle excitatory neurons and thus regulate membrane voltage relevant to the input–output efficacy of these cells. Owing to their robust control of membrane excitability and ubiquitous expression in the hippocampus, their dysfunction can alter network stability in a manner that manifests in recurrent seizures. Indeed, growing evidence implicates these channels in intractable epilepsies of the temporal lobe, which underscores the importance of determining the molecular mechanisms underlying their regulation and contribution to pathologies. Here, we describe the role of p38 kinase phosphorylation of a C-terminal motif in Kv4.2 in modulating hippocampal neuronal excitability and behavioral seizure strength. Using a combination of biochemical, single-cell electrophysiology, and in vivo seizure techniques, we show that kainic acid-induced seizure induces p38-mediated phosphorylation of Thr607 in Kv4.2 in a time-dependent manner. The pharmacological and genetic disruption of this process reduces neuronal excitability and dampens seizure intensity, illuminating a cellular cascade that may be targeted for therapeutic intervention to mitigate seizure intensity and progression.

Q- and L-type calcium channels control the development of calbindin phenotype in hippocampal pyramidal neurons in vitro

2000 ◽  
Vol 12 (6) ◽  
pp. 2068-2078 ◽  
Author(s):  
Hassan Boukhaddaoui ◽  
Victor Sieso ◽  
Frédérique Scamps ◽  
Stephan Vigues ◽  
Anne Roig ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Pyramidal Neurons ◽  
Hippocampal Pyramidal Neurons

scholarly journals Two modes of inhibitory neuronal shutdown distinctly amplify seizures in humans

2020 ◽  
Author(s):  
Omar J. Ahmed ◽  
Tibin T. John ◽  
Shyam K. Sudhakar ◽  
Ellen K.W. Brennan ◽  
Alcides Lorenzo Gonzalez ◽  
...  
Keyword(s):  
Brain Function ◽  
Action Potentials ◽  
Computational Models ◽  
Neuronal Firing ◽  
Inhibitory Neurons ◽  
Normal Brain ◽  
Neuronal Control ◽  
Normal Brain Function ◽  
Fast Spiking

ABSTRACTInhibitory neurons are critical for normal brain function but dysregulated in disorders such as epilepsy. At least two theories exist for how inhibition may acutely decrease during a seizure: hyperpolarization of fast-spiking (FS) inhibitory neurons by other inhibitory neurons, or depolarization block (DB) of FS neurons resulting in an inability to fire action potentials. Firing rate alone is unable to disambiguate these alternatives. Here, we show that human FS neurons can stop firing due to both hyperpolarization and DB within the same seizure. However, only DB of FS cells is associated with dramatic increases in local seizure amplitude, unobstructed traveling waves, and transient increases in excitatory neuronal firing. This result is independent of seizure etiology or focus. Computational models of DB reproduce the in vivo human biophysics. These methods enable intracellular decoding using only extracellular recordings in humans and explain the otherwise ambiguous inhibitory neuronal control of human seizures.

scholarly journals Sleep loss drives brain region- and cell type-specific alterations in ribosome-associated transcripts involved in synaptic plasticity and cellular timekeeping

2020 ◽  
Author(s):  
Carlos Puentes-Mestril ◽  
James Delorme ◽  
Marcus Donnelly ◽  
Donald Popke ◽  
Sha Jiang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Brain Region ◽  
Pyramidal Neurons ◽  
Affinity Purification ◽  
Protein Translation ◽  
Sleep Loss ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Mouse Hippocampus ◽  
Excitatory Neurons

AbstractSleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex - for example, in inhibitory vs. excitatory neurons. Here we use translating ribosome affinity purification (TRAP) and in situ hybridization to characterize the effects of sleep vs. SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a+) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in mouse hippocampus and neocortex. We find that while both Camk2a+ neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected by SD in hippocampus. Similarly we find that while SD alters several ribosome-associated transcripts involved in cellular timekeeping in neocortical Camk2a+ and PV+ neurons, effects on circadian clock transcripts in hippocampus are minimal, and restricted to Camk2a+ neurons. Taken together, our results indicate that SD effects on transcripts destined for translation are both cell type- and brain region-specific, and that these effects are substantially more pronounced in the neocortex than the hippocampus. We conclude that SD-driven alterations in the strength of synapses, excitatory-inhibitory balance, and cellular timekeeping are likely more heterogeneous than previously appreciated.Significance StatementSleep loss-driven changes in transcript and protein abundance have been used as a means to better understand the function of sleep for the brain. Here we use translating ribosome affinity purification (TRAP) to characterize changes in abundance of ribosome-associated transcripts in excitatory and inhibitory neurons in mouse hippocampus and neocortex after a brief period of sleep or sleep loss. We show that these changes are not uniform, but are generally more pronounced in excitatory neurons than inhibitory neurons, and more pronounced in neocortex than in hippocampus.

Ca2+ Channels Involved in the Generation of the Slow Afterhyperpolarization in Cultured Rat Hippocampal Pyramidal Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2554-2561 ◽  
Author(s):  
M. Shah ◽  
D. G. Haylett
Keyword(s):  
Calcium Channels ◽  
Action Potentials ◽  
Calcium Release ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Isolated Cells ◽  
Hippocampal Pyramidal Neurons ◽  
Calcium Induced Calcium Release ◽  
Ca2 Channels ◽  
Hippocampal Pyramidal Cells

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (m I AHP and s I AHP, respectively) could be obtained from pyramidal cells that were cultured for 8–15 days. The s I AHP demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the s I AHP is also insensitive to 100 nM charybdotoxin but is inhibited by 100 μMd-tubocurarine. Concentrations of nifedipine (10 μM) and nimodipine (3 μM) that maximally inhibit L-type calcium channels reduced the s I AHP by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 μM) abolished the s I AHP, which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, ω-conotoxin GVIA (100 nM), irreversibly inhibited the s I AHP by 37%. Together, ω-conotoxin (100 nM) and nifedipine (10 μM) inhibited the s I AHP by 70%. 10 μM ryanodine also reduced the s I AHP by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the s I AHP in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.

scholarly journals Reelin Affects Signaling Pathways of a Group of Inhibitory Neurons and the Development of Inhibitory Synapses in Primary Neurons

2021 ◽  
Vol 22 (14) ◽  
pp. 7510
Author(s):  
Gum Hwa Lee ◽  
Seong-Eun Lee
Keyword(s):  
Hippocampal Neurons ◽  
Secretory Protein ◽  
Protein Supplementation ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Cellular Mechanisms ◽  
Dendrite Development ◽  
Excitatory Neurons ◽  
And Function

Reelin is a secretory protein involved in a variety of processes in forebrain development and function, including neuronal migration, dendrite growth, spine formation, and synaptic plasticity. Most of the function of Reelin is focused on excitatory neurons; however, little is known about its effects on inhibitory neurons and inhibitory synapses. In this study, we investigated the phosphatidylinositol 3-kinase/Akt pathway of Reelin in primary cortical and hippocampal neurons. Individual neurons were visualized using immunofluorescence to distinguish inhibitory neurons from excitatory neurons. Reelin-rich protein supplementation significantly induced the phosphorylation of Akt and ribosomal S6 protein in excitatory neurons, but not in most inhibitory neurons. In somatostatin-expressing inhibitory neurons, one of major subtypes of inhibitory neurons, Reelin-rich protein supplementation induced the phosphorylation of S6. Subsequently, we investigated whether or not Reelin-rich protein supplementation affected dendrite development in cultured inhibitory neurons. Reelin-rich protein supplementation did not change the total length of dendrites in inhibitory neurons in vitro. Finally, we examined the development of inhibitory synapses in primary hippocampal neurons and found that Reelin-rich protein supplementation significantly reduced the density of gephyrin–VGAT-positive clusters in the dendritic regions without changing the expression levels of several inhibitory synapse-related proteins. These findings indicate a new role for Reelin in specific groups of inhibitory neurons and the development of inhibitory synapses, which may contribute to the underlying cellular mechanisms of RELN-associated neurological disorders.

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