Asymmetry and modulation of spike timing in electrically coupled neurons

2015 ◽  
Vol 113 (6) ◽  
pp. 1743-1751 ◽  
Author(s):  
Jessica Sevetson ◽  
Julie S. Haas
Keyword(s):  
Critical Role ◽  
Electrical Coupling ◽  
Brain Slices ◽  
Spike Timing ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Electrical Synapses ◽  
Thalamic Relay ◽  
Coupled Networks ◽  
The Brain

Electrical coupling mediates interactions between neurons of the thalamic reticular nucleus (TRN), which play a critical role in regulating thalamocortical and corticothalamic communication by inhibiting thalamic relay cells. Accumulating evidence has shown that asymmetry of electrical synapses is a fundamental and dynamic property, but the effect of asymmetry on coupled networks is unexplored. Recording from patched pairs in rat brain slices, we investigate asymmetry in the subthreshold regime and show that electrical synapses can exert powerful effects on the spike times of coupled neighbors. Electrical synaptic signaling modulates spike timing by 10–20 ms, in an effect that also exhibits asymmetry. Furthermore, we show through modeling that coupling asymmetry expands the set of outputs for pairs of coupled neurons through enhanced regions of synchrony and reversals of spike order. These results highlight the power and specificity of signaling exerted by electrical synapses, which contribute to information flow across the brain.

scholarly journals Electrical synapses between inhibitory neurons shape the responses of principal neurons to transient inputs in the thalamus

2017 ◽  
Author(s):  
Tuan Pham ◽  
Julie S. Haas
Keyword(s):  
Cell Model ◽  
Sensory Information ◽  
Spike Trains ◽  
Inhibitory Neurons ◽  
Reticular Nucleus ◽  
Electrical Synapses ◽  
Thalamic Relay ◽  
Transient Activity ◽  
The Impact ◽  
The Brain

AbstractAs multimodal sensory information proceeds to the cortex, it is intercepted and processed by the nuclei of the thalamus. The main source of inhibition within thalamus is the reticular nucleus (TRN), which collects signals both from thalamocortical relay neurons and from thalamocortical feedback. Within the reticular nucleus, neurons are densely interconnected by connexin36-based gap junctions, known as electrical synapses. Electrical synapses have been shown to coordinate neuronal rhythms, including thalamocortical spindle rhythms, but their role in shaping or modulating transient activity is less understood. We constructed a four-cell model of thalamic relay and TRN neurons, and used it to investigate the impact of electrical synapses on closely timed inputs delivered to thalamic relay cells. We show that the electrical synapses of the TRN assist cortical discrimination of these inputs through effects of truncation, delay or inhibition of thalamic spike trains. We expect that these are principles whereby electrical synapses play similar roles in processing of transient activity in excitatory neurons across the brain.

scholarly journals Fluidic microactuation of flexible electrodes for neural recording

2017 ◽  
Author(s):  
Flavia Vitale ◽  
Daniel G. Vercosa ◽  
Alexander V. Rodriguez ◽  
Sushma Sri Pamulapati ◽  
Frederik Seibt ◽  
...  
Keyword(s):  
Action Potentials ◽  
Brain Slices ◽  
Model Organism ◽  
Cell Loss ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Electrode Position ◽  
Flexible Electrodes ◽  
Carbon Nanotube Fiber ◽  
The Brain

Ultra-flexible microelectrodes that can bend and flex with the natural movement of the brain reduce the inflammatory response and improve the stability of long-term neural recordings.1-5However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that increase the electrode size6-10thus aggravating neural damage during implantation, which leads to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve.11-13A method to deliver thin, ultra-flexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultra-flexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these “fluidic microdrives” allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes11,14for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarianHydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically-evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the injection site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultra-flexible neural electrodes.

Mapping of the Functional Interconnections Between Thalamic Reticular Neurons Using Photostimulation

2006 ◽  
Vol 96 (5) ◽  
pp. 2593-2600 ◽  
Author(s):  
Ying-Wan Lam ◽  
Christopher S. Nelson ◽  
S. Murray Sherman
Keyword(s):  
Laser Scanning ◽  
Spatial Extent ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Reticular Cell ◽  
Relay Cell ◽  
Dominant Form ◽  
Electrical Synapses ◽  
Reticular Neurons ◽  
Reticular Cells

The thalamic reticular nucleus is strategically located in the axonal pathways between thalamus and cortex, and reticular cells exert strong, topographic inhibition on thalamic relay cells. Although evidence exists that reticular neurons are interconnected through conventional and electrical synapses, the spatial extent and relative strength of these synapses are unclear. To address these issues, we used uncaging of glutamate by laser-scanning photostimulation to provide precisely localized and consistent activation of reticular cell bodies and dendrites in an in vitro slice preparation from the rat as a means to study reticulo-reticular connections. Among the 47 recorded reticular neurons, 29 (62%) received GABAergic axodendritic input from an area immediately surrounding each of the recorded cell bodies, and 8 (17%) responded with depolarizing spikelets, suggesting inputs through electrical synapses. We also found that TTX completely blocked all evoked IPSCs, implying that any dendrodendritic synapses between reticular cells either are relatively weak, have no nearby glutamatergic receptors, or are dependent on back-propagation of action potentials. Finally, we showed that the GABAergic connections between reticular cells are weaker than those from reticular cells to relay cells. Our results suggest that the GABAergic axodendritic synapse is the dominant form of reticulo-reticular connectivity, and because they are much weaker than the reticulo-relay cell synapses, their functional purpose may be to regulate the spatial extent of the reticular inhibition on relay cells.

scholarly journals Significance of the Thalamic Reticular Nucleus GABAergic Neurons in Normal and Pathological Activity of the Brain

2012 ◽  
Vol 02 (04) ◽  
pp. 436-444 ◽  
Author(s):  
Zakaria I. Nanobashvili ◽  
Arkadi G. Surmava ◽  
Irine G. Bilanishvili ◽  
Maia G. Barbaqadze ◽  
Magda D. Mariamidze ◽  
...  
Keyword(s):  
Gabaergic Neurons ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
The Brain

Anatomic, Intrinsic, and Synaptic Properties of Dorsal and Ventral Division Neurons in Rat Medial Geniculate Body

1999 ◽  
Vol 81 (5) ◽  
pp. 1999-2016 ◽  
Author(s):  
Edward L. Bartlett ◽  
Philip H. Smith
Keyword(s):  
Membrane Potential ◽  
Nmda Receptors ◽  
Brain Slices ◽  
Medial Geniculate Body ◽  
Dendritic Tree ◽  
Dendritic Morphology ◽  
Thalamic Reticular Nucleus ◽  
Membrane Properties ◽  
Reticular Nucleus ◽  
Medial Geniculate

Anatomic, intrinsic, and synaptic properties of dorsal and ventral division neurons in rat medial geniculate body. Presently little is known about what basic synaptic and cellular mechanisms are employed by thalamocortical neurons in the two main divisions of the auditory thalamus to elicit their distinct responses to sound. Using intracellular recording and labeling methods, we characterized anatomic features, membrane properties, and synaptic inputs of thalamocortical neurons in the dorsal (MGD) and ventral (MGV) divisions in brain slices of rat medial geniculate body. Quantitative analysis of dendritic morphology demonstrated that tufted neurons in both divisions had shorter dendrites, smaller dendritic tree areas, more profuse branching, and a greater dendritic polarization compared with stellate neurons, which were only found in MGD. Tufted neuron dendritic polarization was not as strong or consistent as earlier Golgi studies suggested. MGV and MGD cells had similar intrinsic properties except for an increased prevalence of a depolarizing sag potential in MGV neurons. The sag was the only intrinsic property correlated with cell morphology, seen only in tufted neurons in either division. Many MGV and MGD neurons received excitatory and inhibitory inferior colliculus (IC) inputs (designated IN/EX or EX/IN depending on excitation/inhibition sequence). However, a significant number only received excitatory inputs (EX/O) and a few only inhibitory (IN/O). Both MGV and MGD cells displayed similar proportions of response combinations, but suprathreshold EX/O responses only were observed in tufted neurons. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) had multiple distinguishable amplitude levels implying convergence. Excitatory inputs activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors the relative contributions of which were variable. For IN/EX cells with suprathreshold inputs, first-spike timing was independent of membrane potential unlike that of EX/O cells. Stimulation of corticothalamic (CT) and thalamic reticular nucleus (TRN) axons evoked a GABAA IPSP, EPSP, GABAB IPSP sequence in most neurons with both morphologies in both divisions. TRN IPSPs and CT EPSPs were graded in amplitude, again suggesting convergence. CT inputs activated AMPA and NMDA receptors. The NMDA component of both IC and CT inputs had an unusual voltage dependence with a detectable dl-2-amino-5-phosphonovaleric acid-sensitive component even below −70 mV. First-spike latencies of CT evoked action potentials were sensitive to membrane potential regardless of whether the TRN IPSP was present. Overall, our in vitro data indicate that reported regional differences in the in vivo responses of MGV and MGD cells to auditory stimuli are not well correlated with major differences in intrinsic membrane features or synaptic responses between cell types.

scholarly journals Electrical Synapses in the Thalamic Reticular Nucleus

2002 ◽  
Vol 22 (3) ◽  
pp. 1002-1009 ◽  
Author(s):  
Carole E. Landisman ◽  
Michael A. Long ◽  
Michael Beierlein ◽  
Michael R. Deans ◽  
David L. Paul ◽  
...  
Keyword(s):  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Electrical Synapses

scholarly journals Electrical synapse asymmetry results from, and masks, neuronal heterogeneity

2021 ◽  
Author(s):  
Julie Haas ◽  
Austin Mendoza
Keyword(s):  
Electrical Coupling ◽  
Input Resistance ◽  
Spike Timing ◽  
Inhibitory Neurons ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
Intrinsic Factors ◽  
Dendritic Processing ◽  
Coupled Cells ◽  
Dendritic Location

Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many basic functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these is the source and impact of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to synaptic asymmetry and that result in modulation of spike time between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, true synapse asymmetry can be masked by each of these properties. Furthermore, we show that asymmetry alters the spiking timing and latency of coupled cells by up to tens of milliseconds, depending on direction of conduction or dendritic location of the electrical synapse. These simulations illustrate that causes of asymmetry are multifactorial, may not be apparent in somatic measurements of electrical coupling, influence dendritic processing, and produce a variety of outcomes on spike timing of coupled cells. Our findings highlight aspects of electrical synapses that should be considered in experimental demonstrations of coupling, and when assembling networks containing electrical synapses.

scholarly journals Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis

2020 ◽  
Vol 16 (12) ◽  
pp. e1009152
Author(s):  
Chakir Bello ◽  
Yasmine Smail ◽  
Vincent Sainte-Rose ◽  
Isabelle Podglajen ◽  
Alice Gilbert ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Connexin 43 ◽  
Critical Role ◽  
Neurovascular Unit ◽  
Brain Slices ◽  
Host Cells ◽  
Intermediate Filament Protein ◽  
Young Infants ◽  
The Brain

Streptococcus pneumoniae or pneumococcus (PN) is a major causative agent of bacterial meningitis with high mortality in young infants and elderly people worldwide. The mechanism underlying PN crossing of the blood brain barrier (BBB) and specifically, the role of non-endothelial cells of the neurovascular unit that control the BBB function, remains poorly understood. Here, we show that the astroglial connexin 43 (aCx43), a major gap junctional component expressed in astrocytes, plays a predominant role during PN meningitis. Following intravenous PN challenge, mice deficient for aCx43 developed milder symptoms and showed severely reduced bacterial counts in the brain. Immunofluorescence analysis of brain slices indicated that PN induces the aCx43–dependent destruction of the network of glial fibrillary acid protein (GFAP), an intermediate filament protein specifically expressed in astrocytes and up-regulated in response to brain injury. PN also induced nuclear shrinkage in astrocytes associated with the loss of BBB integrity, bacterial translocation across endothelial vessels and replication in the brain cortex. We found that aCx4-dependent astrocyte damages could be recapitulated using in vitro cultured cells upon challenge with wild-type PN but not with a ply mutant deficient for the pore-forming toxin pneumolysin (Ply). Consistently, we showed that purified Ply requires Cx43 to promote host cell plasma membrane permeabilization in a process involving the Cx43-dependent release of extracellular ATP and prolonged increase of cytosolic Ca2+ in host cells. These results point to a critical role for astrocytes during PN meningitis and suggest that the cytolytic activity of the major virulence factor Ply at concentrations relevant to bacterial infection requires co-opting of connexin plasma membrane channels.

scholarly journals Differential inputs to striatal cholinergic and parvalbumin interneurons imply functional distinctions

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jason R Klug ◽  
Max D Engelhardt ◽  
Cara N Cadman ◽  
Hao Li ◽  
Jared B Smith ◽  
...  
Keyword(s):  
Pedunculopontine Nucleus ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Cortical Input ◽  
Parvalbumin Interneurons ◽  
Controlling Behavior ◽  
Health And Disease ◽  
Striatal Interneurons ◽  
Striatal Function ◽  
The Brain

Striatal cholinergic (ChAT) and parvalbumin (PV) interneurons exert powerful influences on striatal function in health and disease, yet little is known about the organization of their inputs. Here using rabies tracing, electrophysiology and genetic tools, we compare the whole-brain inputs to these two types of striatal interneurons and dissect their functional connectivity in mice. ChAT interneurons receive a substantial cortical input from associative regions of cortex, such as the orbitofrontal cortex. Amongst subcortical inputs, a previously unknown inhibitory thalamic reticular nucleus input to striatal PV interneurons is identified. Additionally, the external segment of the globus pallidus targets striatal ChAT interneurons, which is sufficient to inhibit tonic ChAT interneuron firing. Finally, we describe a novel excitatory pathway from the pedunculopontine nucleus that innervates ChAT interneurons. These results establish the brain-wide direct inputs of two major types of striatal interneurons and allude to distinct roles in regulating striatal activity and controlling behavior.

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