Recruitment of GABAergic Inhibition and Synchronization of Inhibitory Interneurons in Rat Neocortex

Benardo, Larry S. Recruitment of GABAergic inhibition and synchronization of inhibitory interneurons in rat neocortex. J. Neurophysiol. 77: 3134–3144, 1997. Intracellular recordings were obtained from pyramidal and interneuronal cells in rat neocortical slices to examine the recruitment of GABAergic inhibition and inhibitory interneurons. In the presence of the convulsant agent4-aminopyridine (4-AP), after excitatory amino acid (EAA) ionotropic transmission was blocked, large-amplitude triphasic inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 10–40 s) and synchronously in pyramidal neurons. After exposure to the γ-aminobutyric acid-A (GABAA) receptor antagonist picrotoxin, large-amplitude monophasic slow IPSPs persisted in these cells. In the presence of 4-AP and EAA blockers, interneurons showed periodic spike firing. Although some spikes rode on an underlying synaptic depolarization, much of the rhythmic firing consisted of spikes having highly variable amplitudes, arising abruptly from baseline, even during hyperpolarization. The spike firing and depolarizing synaptic potentials were completely suppressed by picrotoxin exposure, although monophasic slow IPSPs persisted in interneurons. This suggests that this subset of interneurons may participate in generating fast GABAA IPSPs, but not slow GABAB IPSPs. Cell morphology was confirmed by intracellular injection of neurobiotin or the fluorescent dye Lucifer yellow CH. Dye injection into interneurons often (>70%) resulted in the labeling of two to six cells (dye coupling). These findings suggest that GABAAergic neurons may be synchronized via recurrent collaterals through the depolarizing action of synaptically activatedGABAA receptors and a mechanism involving electrotonic coupling. Although inhibitory neurons mediating GABAB IPSPs may be entrained by the excitatory GABAA mechanism, they appear to be a separate subset of GABAergic neurons capable of functioning independently with autonomous pacing.

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Specificity of Synaptic Connectivity between Layer 1 Inhibitory Interneurons and Layer 2/3 Pyramidal Neurons in the Rat Neocortex

Cerebral Cortex ◽

10.1093/cercor/bhq257 ◽

2011 ◽

Vol 21 (8) ◽

pp. 1818-1826 ◽

Cited By ~ 80

Author(s):

Christian Wozny ◽

Stephen R. Williams

Keyword(s):

Pyramidal Neurons ◽

Synaptic Connectivity ◽

Inhibitory Interneurons ◽

Layer 2 ◽

Rat Neocortex

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Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and inhibitory interneurons

10.1101/2021.04.04.438418 ◽

2021 ◽

Author(s):

Joshua B. Melander ◽

Aran Nayebi ◽

Bart C. Jongbloets ◽

Dale A. Fortin ◽

Maozhen Qin ◽

...

Keyword(s):

Pyramidal Neurons ◽

Synaptic Weight ◽

Barrel Cortex ◽

Inhibitory Neurons ◽

Inhibitory Interneurons ◽

Excitatory Synapses ◽

Cell Type ◽

Cortical Function ◽

Cell Type Specific

SUMMARYCortical function relies on the balanced activation of excitatory and inhibitory neurons. However, little is known about the organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneurons, which cannot be easily identified morphologically. Here, we fluorescently visualize the excitatory postsynaptic marker PSD-95 at endogenous levels as a proxy for excitatory synapses onto layer 2/3 pyramidal neurons and parvalbumin-positive (PV+) inhibitory interneurons in the mouse barrel cortex. Longitudinal in vivo imaging reveals that, while synaptic weights in both neuronal types are log-normally distributed, synapses onto PV+ neurons are less heterogeneous and more stable. Markov-model analyses suggest that the synaptic weight distribution is set intrinsically by ongoing cell type-specific dynamics, and substantial changes are due to accumulated gradual changes. Synaptic weight dynamics are multiplicative, i.e., changes scale with weights, though PV+ synapses also exhibit an additive component. These results reveal that cell type-specific processes govern cortical synaptic strengths and dynamics.

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Dynamics of the CA3 pyramidial neuron autoassociative memory network in the hippocampus

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1994.0019 ◽

1994 ◽

Vol 343 (1304) ◽

pp. 167-187 ◽

Cited By ~ 52

Keyword(s):

Pyramidal Neurons ◽

Pyramidal Cells ◽

Recurrent Network ◽

Inhibitory Neurons ◽

Regulatory Function ◽

Inhibitory Interneurons ◽

Spatial Correlations ◽

Temporal Correlations ◽

Recurrent Collateral ◽

Ca3 Region

A theory for the dynamics of sparse associative memory has been applied to the CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as a network of pyramidal neurons randomly connected through their recurrent collaterals. Both the elliptical spread of the axonal systems and the exponential decrease in connectivity with distance are taken into account in estimating the connection probabilities. Pyramidal neurons also receive connections from inhibitory interneurons which occur in large numbers throughout the network; these in turn receive inputs from other inhibitory interneurons and from pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear devices which produce outputs proportional to their inputs; they perform an important regulatory function in the setting of the membrane potentials of the pyramidal neurons. The probability of a neuron firing in a stored memory, which determines the average number of neurons active when a memory is recalled, can be set at will. Memories are stored at the recurrent collateral synapses using a two-valued Hebbian. Allowance is made in the theory both for the spatial correlations between the learned strengths of the recurrent collateral synapses and temporal correlations between the state of the network and these synaptic strengths. The recall of a memory begins with the firing of a set of CA3 pyramidal neurons that overlap with the memory to be recalled as well as the firing of a set of pyramidal neurons not in the memory to be recalled; the firing of both sets of neurons is probably induced by synapses formed on CA3 neurons by perforant pathway axons. The firing of different sets of pyram idal neurons then evolves by discrete synchronous steps. The CA3 recurrent network is shown to retrieve memories under specific conditions of the setting of the membrane potential of the pyramidal neurons by inhibitory interneurons. The adjustable parameters in the theory have been assigned values in accord with the known physiology of the CA3 region. Certain levels of overlap between the input and the memory to be retrieved must also be satisfied for almost complete retrieval. The number of memories which can be stored and retrieved without degradation is primarily a function of the number of active neurons when a memory is recalled and the degree of connectivity in the network. The inhomogeneity in the connectivity of the pyramidal cells improves both capacity and overlap of the final state with the memory. T he probabilistic secretion of quanta at the recurrent collateral synapses improves the recall mechanism when there is only partial overlap in the input with the memory to be retrieved and the input contains incorrect elements, at the expense of a slight deterioration in the fidelity of recall.

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Organization of cortical and thalamic input to inhibitory neurons in mouse motor cortex

10.1101/2021.07.08.451716 ◽

2021 ◽

Author(s):

Sandra U Okoro ◽

Roman U Goz ◽

Brigdet W. Njeri ◽

Madhumita Harish ◽

Catherine F. Ruff ◽

...

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Inhibitory Neurons ◽

Inhibitory Interneurons ◽

Thalamic Input ◽

Thalamic Projections ◽

A Cell ◽

Feedforward Inhibition

Understanding how feedforward inhibition regulates movement requires knowing how cortical and thalamic projections connect to inhibitory interneurons in primary motor cortex (M1). We quantified excitatory synaptic input from sensory cortex and thalamus onto two main classes of M1 inhibitory interneurons across all cortical layers: parvalbumin (PV) expressing fast-spiking cells and somatostatin (SOM) expressing low-threshold-spiking cells. Each projection innervated M1 interneurons with a unique laminar profile. While pyramidal neurons were excited by these cortical and thalamic inputs in the same layers, different interneuron types were excited in a distinct, complementary manner, suggesting feedforward inhibition from different inputs proceeds selectively via distinct circuits. Specifically, somatosensory cortex (S1) inputs primarily targeted PV+ neurons in upper layers (L2/3) but SOM+ neurons in middle layers (L5). Somatosensory thalamus (PO) inputs primarily targeted PV+ neurons in middle layers (L5). Our results show that long-range excitatory inputs target inhibitory neurons in a cell type-specific manner which contrasts with input to neighboring pyramidal cells. In contrast to feedforward inhibition providing generic inhibitory tone in cortex, circuits are selectively organized to recruit inhibition matched to incoming excitatory circuits.

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

10.1101/2022.01.13.476247 ◽

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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Widely Different Correlation Patterns Between Pairs of Adjacent Thalamic Neurons In vivo

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.692923 ◽

2021 ◽

Vol 15 ◽

Author(s):

Anders Wahlbom ◽

Hannes Mogensen ◽

Henrik Jörntell

Keyword(s):

Cortical Neurons ◽

Pyramidal Neurons ◽

Thalamic Nuclei ◽

Thalamic Neurons ◽

Low Weight ◽

Afferent Inputs ◽

Cortical Inputs ◽

Unique Relationship ◽

Spike Firing

We have previously reported different spike firing correlation patterns among pairs of adjacent pyramidal neurons within the same layer of S1 cortex in vivo, which was argued to suggest that acquired synaptic weight modifications would tend to differentiate adjacent cortical neurons despite them having access to near-identical afferent inputs. Here we made simultaneous single-electrode loose patch-clamp recordings from 14 pairs of adjacent neurons in the lateral thalamus of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing. As the synapses on thalamic neurons are dominated by a high number of low weight cortical inputs, which would be expected to be shared for two adjacent neurons, and as far as thalamic neurons have homogenous membrane physiology and spike generation, they would be expected to have overall similar spike firing and therefore also correlation patterns. However, we find that across a variety of thalamic nuclei the correlation patterns between pairs of adjacent thalamic neurons vary widely. The findings suggest that the connectivity and cellular physiology of the thalamocortical circuitry, in contrast to what would be expected from a straightforward interpretation of corticothalamic maps and uniform intrinsic cellular neurophysiology, has been shaped by learning to the extent that each pair of thalamic neuron has a unique relationship in their spike firing activity.

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Features Of Hippocampal Astrocytic Domains And Their Spatial Relation To Excitatory And Inhibitory Neurons

10.1101/2020.05.25.114348 ◽

2020 ◽

Author(s):

Ron Refaeli ◽

Adi Doron ◽

Aviya Benmelech-Chovav ◽

Maya Groysman ◽

Tirzah Kreisel ◽

...

Keyword(s):

Spatial Distribution ◽

Pyramidal Neurons ◽

Spatial Relation ◽

Design Principles ◽

Inhibitory Neurons ◽

Computational Tools ◽

Close Proximity ◽

Somatostatin Neurons ◽

And Behavior ◽

Elaborate Structure

SUMMARYThe mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in cleared hippocampi, and employed converging genetic, histological and computational tools to determine the elaborate structure, distribution and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the detailed morphology of thousands of reconstructed domains. We then determined the excitatory content of CA1 astrocytes, averaging above 13 pyramidal neurons per domain and increasing towards CA1 midline. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This resource expands our understanding of fundamental hippocampal design principles, and provides the first quantitative foundation for neuron-astrocyte interactions in this region.

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Muscarinic Acetylcholine Receptor Localization on Distinct Excitatory and Inhibitory Neurons Within the ACC and LPFC of the Rhesus Monkey

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.795325 ◽

2022 ◽

Vol 15 ◽

Author(s):

Alexandra Tsolias ◽

Maria Medalla

Keyword(s):

Prefrontal Cortex ◽

Muscarinic Receptors ◽

Calcium Binding ◽

Pyramidal Neurons ◽

Muscarinic Acetylcholine Receptor ◽

Anterior Cingulate ◽

Inhibitory Neurons ◽

Receptor Localization ◽

Cortical Inputs ◽

Almost All

Acetylcholine (ACh) can act on pre- and post-synaptic muscarinic receptors (mAChR) in the cortex to influence a myriad of cognitive processes. Two functionally-distinct regions of the prefrontal cortex—the lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC)—are differentially innervated by ascending cholinergic pathways yet, the nature and organization of prefrontal-cholinergic circuitry in primates are not well understood. Using multi-channel immunohistochemical labeling and high-resolution microscopy, we found regional and laminar differences in the subcellular localization and the densities of excitatory and inhibitory subpopulations expressing m1 and m2 muscarinic receptors, the two predominant cortical mAChR subtypes, in the supragranular layers of LPFC and ACC in rhesus monkeys (Macaca mulatta). The subset of m1+/m2+ expressing SMI-32+ pyramidal neurons labeled in layer 3 (L3) was denser in LPFC than in ACC, while m1+/m2+ SMI-32+ neurons co-expressing the calcium-binding protein, calbindin (CB) was greater in ACC. Further, we found between-area differences in laminar m1+ dendritic expression, and m2+ presynaptic localization on cortico-cortical (VGLUT1+) and sub-cortical inputs (VGLUT2+), suggesting differential cholinergic modulation of top-down vs. bottom-up inputs in the two areas. While almost all inhibitory interneurons—identified by their expression of parvalbumin (PV+), CB+, and calretinin (CR+)—expressed m1+, the localization of m2+ differed by subtype and area. The ACC exhibited a greater proportion of m2+ inhibitory neurons compared to the LPFC and had a greater density of presynaptic m2+ localized on inhibitory (VGAT+) inputs targeting proximal somatodendritic compartments and axon initial segments of L3 pyramidal neurons. These data suggest a greater capacity for m2+-mediated cholinergic suppression of inhibition in the ACC compared to the LPFC. The anatomical localization of muscarinic receptors on ACC and LPFC micro-circuits shown here contributes to our understanding of diverse cholinergic neuromodulation of functionally-distinct prefrontal areas involved in goal-directed behavior, and how these interactions maybe disrupted in neuropsychiatric and neurological conditions.

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Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the rat dorsal hippocampus

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-005 ◽

1989 ◽

Vol 67 (1) ◽

pp. 29-33 ◽

Cited By ~ 100

Author(s):

Guy Debonnel ◽

Luc Beauchesne ◽

Claude de Montigny

Keyword(s):

Amino Acid ◽

Domoic Acid ◽

Pyramidal Neurons ◽

Excitatory Amino Acid ◽

Dorsal Hippocampus ◽

Electrophysiological Study ◽

Receptor Activation ◽

Kainate Receptor ◽

Neurotoxic Effect ◽

Excitatory Effect

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.Key words: domoate, kainate, excitotoxin, hippocampus, N-methyl-D-aspartate.

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