scholarly journals Response to coincident inputs in electrically coupled primary afferents is heterogeneous and is enhanced by H-current (IH) modulation

2019 ◽  
Vol 122 (1) ◽  
pp. 151-175
Author(s):  
Federico Davoine ◽  
Sebastian Curti
Keyword(s):  
Neuronal Excitability ◽  
Signal To Noise Ratio ◽  
Electrical Coupling ◽  
Primary Afferents ◽  
Coincidence Detection ◽  
Mammalian Brain ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Electrophysiological Properties ◽  
Cationic Current

Electrical synapses represent a widespread modality of interneuronal communication in the mammalian brain. These contacts, by lowering the effectiveness of random or temporally uncorrelated inputs, endow circuits of coupled neurons with the ability to selectively respond to simultaneous depolarizations. This mechanism may support coincidence detection, a property involved in sensory perception, organization of motor outputs, and improvement signal-to-noise ratio. While the role of electrical coupling is well established, little is known about the contribution of the cellular excitability and its modulations to the susceptibility of groups of neurons to coincident inputs. Here, we obtained dual whole cell patch-clamp recordings of pairs of mesencephalic trigeminal (MesV) neurons in brainstem slices from rats to evaluate coincidence detection and its determinants. MesV neurons are primary afferents involved in the organization of orofacial behaviors whose cell bodies are electrically coupled mainly in pairs through soma-somatic gap junctions. We found that coincidence detection is highly heterogeneous across the population of coupled neurons. Furthermore, combined electrophysiological and modeling approaches reveal that this heterogeneity arises from the diversity of MesV neuron intrinsic excitability. Consistently, increasing these cells’ excitability by upregulating the hyperpolarization-activated cationic current ( IH) triggered by cGMP results in a dramatic enhancement of the susceptibility of coupled neurons to coincident inputs. In conclusion, the ability of coupled neurons to detect coincident inputs is critically shaped by their intrinsic electrophysiological properties, emphasizing the relevance of neuronal excitability for the many functional operations supported by electrical transmission in mammals. NEW & NOTEWORTHY We show that the susceptibility of pairs of coupled mesencephalic trigeminal (MesV) neurons to coincident inputs is highly heterogenous and depends on the interaction between electrical coupling and neuronal excitability. Additionally, upregulating the hyperpolarization-activated cationic current ( IH) by cGMP results in a dramatic increase of this susceptibility. The IH and electrical synapses have been shown to coexist in many neuronal populations, suggesting that modulation of this conductance could represent a common strategy to regulate circuit operation supported by electrical coupling.

scholarly journals Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms

2021 ◽  
Author(s):  
Sebastian Curti ◽  
Federico Davoine ◽  
Antonella Dapino
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Brain ◽  
Synaptic Membrane ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Theoretical Evidence ◽  
Circuit Function

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

scholarly journals Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 81
Author(s):  
Sebastian Curti ◽  
Federico Davoine ◽  
Antonella Dapino
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Brain ◽  
Synaptic Membrane ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Electrophysiological Properties ◽  
Theoretical Evidence ◽  
Circuit Function ◽  
Lateral Excitation

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals, they are mostly composed of the protein connexin36. Circuits of electrically coupled neurons are widespread in these animals. Plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations such as lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on the gap junction resistance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage and ligand gated channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here, we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

scholarly journals Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission

2011 ◽  
Vol 106 (2) ◽  
pp. 680-689 ◽  
Author(s):  
Colin G. Evans ◽  
Bjoern Ch. Ludwar ◽  
Timothy Kang ◽  
Elizabeth C. Cropper
Keyword(s):  
Membrane Potential ◽  
Synaptic Transmission ◽  
Electrical Coupling ◽  
Mammalian Brain ◽  
Resting Membrane Potential ◽  
Presynaptic Membrane ◽  
Electrical Transmission ◽  
A Cell ◽  
Peripheral Activation ◽  
Chemical Transmission

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential.

scholarly journals Opioids potentiate electrical transmission at mixed synapses on the Mauthner cell

2015 ◽  
Vol 114 (1) ◽  
pp. 689-697 ◽  
Author(s):  
Roger Cachope ◽  
Alberto E. Pereda
Keyword(s):  
Opioid Receptors ◽  
Mammalian Brain ◽  
Mu Opioid Receptors ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Mu Opioid ◽  
Mauthner Cell ◽  
Connexin 36 ◽  
Mixed Synapses ◽  
Lateral Dendrite

Opioid receptors were shown to modulate a variety of cellular processes in the vertebrate central nervous system, including synaptic transmission. While the effects of opioid receptors on chemically mediated transmission have been extensively investigated, little is known of their actions on gap junction-mediated electrical synapses. Here we report that pharmacological activation of mu-opioid receptors led to a long-term enhancement of electrical (and glutamatergic) transmission at identifiable mixed synapses on the goldfish Mauthner cells. The effect also required activation of both dopamine D1/5 receptors and postsynaptic cAMP-dependent protein kinase A, suggesting that opioid-evoked actions are mediated indirectly via the release of dopamine from varicosities known to be located in the vicinity of the synaptic contacts. Moreover, inhibitory inputs situated in the immediate vicinity of these excitatory synapses on the lateral dendrite of the Mauthner cell were not affected by activation of mu-opioid receptors, indicating that their actions are restricted to electrical and glutamatergic transmissions co-existing at mixed contacts. Thus, as their chemical counterparts, electrical synapses can be a target for the modulatory actions of the opioid system. Because gap junctions at these mixed synapses are formed by fish homologs of the neuronal connexin 36, which is widespread in mammalian brain, it is likely that this regulatory property applies to electrical synapses elsewhere as well.

Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions

1995 ◽  
Vol 75 (4) ◽  
pp. 689-723 ◽  
Author(s):  
J. G. Jefferys
Keyword(s):  
Electric Fields ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Physiological Activity ◽  
Electrical Coupling ◽  
Epileptic Seizures ◽  
Mammalian Brain ◽  
Chemical Coupling ◽  
Extracellular Ions ◽  
Chemical Synapses

Nonsynaptic interactions between neurons have been eclipsed by our increasingly detailed understanding of chemical synapses, but they do play significant roles in the nervous system. This review considers four classes of nonsynaptic interaction, mainly in mammalian brain. 1) Electrotonic (and chemical) coupling through gap junctions has effects during development and under some, often pathological, conditions in the mature brain. 2) Ephaptic transmission is mediated by electrical coupling between specific neuronal elements in the absence of specialized contacts, notably in the cerebellum, and in axon tracts affected by demyelination. 3) Field effect interactions are mediated by large extracellular currents and potential fields generated by the hippocampus and other cortical structures. Both endogenous and applied electric fields alter neuronal excitability at field strengths over a few millivolts per millimeter. Weaker fields have more subtle effects, for instance, on axonal growth during development and repair and, more controversially, in behavioral responses to environmental fields. 4) There are fluctuations in extracellular ions such as K+, which are released during neuronal activity and which alter neuronal excitability. Field effects and ion fluctuations probably have modest effects during physiological activity but have a significant impact on epileptic seizures, and can sustain them in the absence of synaptic transmission.

Interspike interval analysis and spikelets in presubicular head-direction cells

2018 ◽  
Vol 120 (2) ◽  
pp. 564-575 ◽  
Author(s):  
Stefano Coletta ◽  
Roxana Zeraati ◽  
Khaled Nasr ◽  
Patricia Preston-Ferrer ◽  
Andrea Burgalossi
Keyword(s):  
Signal To Noise Ratio ◽  
Mammalian Brain ◽  
High Signal ◽  
Head Direction ◽  
Interspike Intervals ◽  
Electrophysiological Properties ◽  
Specific Direction ◽  
Highly Correlated ◽  
Internal Sense ◽  
Spike Bursts

Head-direction (HD) neurons are thought to provide the mammalian brain with an internal sense of direction. These cells, which selectively increase their firing when the animal’s head points in a specific direction, use the spike rate to encode HD with a high signal-to-noise ratio. In the present work, we analyzed spike train features of presubicular HD cells recorded juxtacellularly in passively rotated rats. We found that HD neurons could be classified into two groups on the basis of their propensity to fire spikes at short interspike intervals. “Bursty” neurons displayed distinct spike waveforms and were weakly but significantly more modulated by HD compared with “nonbursty” cells. In a subset of HD neurons, we observed the occurrence of spikelets, small-amplitude “spike-like” events, whose HD tuning was highly correlated to that of the co-recorded juxtacellular spikes. Bursty and nonbursty HD cells, as well as spikelets, were also observed in freely moving animals during natural behavior. We speculate that spike bursts and spikelets might contribute to presubicular HD coding by enhancing its accuracy and transmission reliability to downstream targets. NEW & NOTEWORTHY We provide evidence that presubicular head-direction (HD) cells can be classified into two classes (bursty and nonbursty) on the basis of their propensity to fire spikes at short interspike intervals. Bursty cells displayed distinct electrophysiological properties and stronger directional tuning compared with nonbursty neurons. We also provide evidence for the occurrence of spikelets in a subset of HD cells. These electrophysiological features (spike bursts and spikelets) might contribute to the precision and robustness of the presubicular HD code.

Enhancement of ITD Coding Within the Initial Stages of the Auditory Pathway

2010 ◽  
Vol 103 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Michael Pecka ◽  
Ida Siveke ◽  
Benedikt Grothe ◽  
Nicholas A. Lesica
Keyword(s):  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Auditory Pathway ◽  
Coincidence Detection ◽  
Mammalian Brain ◽  
Medial Superior Olive ◽  
Interaural Time Differences ◽  
Dorsal Nucleus ◽  
The Individual ◽  
Two Stages

Sensory systems use a variety of strategies to increase the signal-to-noise ratio in their inputs at the receptor level. However, important cues for sound localization are not present at the individual ears but are computed after inputs from the two ears converge within the brain, and we hypothesized that additional strategies to enhance the representation of these cues might be employed in the initial stages after binaural convergence. Specifically, we investigated the transformation that takes place between the first two stages of the gerbil auditory pathway that are sensitive to differences in the arrival time of a sound at the two ears (interaural time differences; ITDs): the medial superior olive (MSO), where ITD tuning originates, and the dorsal nucleus of the lateral lemniscus (DNLL), to which the MSO sends direct projections. We use a combined experimental and computational approach to demonstrate that the coding of ITDs is dramatically enhanced between these two stages, with the mutual information in the responses of single neurons increasing by a factor of 2. We also show that this enhancement is related to an increase in dynamic range for neurons with high preferred frequencies and a decrease in variability for neurons with low preferred frequencies. These results suggest that a major role of the initial stages of the ITD pathway may be to enhance the representation created at the site of coincidence detection and illustrate the potential of this pathway as a model system for the study of strategies for enhancing sensory representations in the mammalian brain.

scholarly journals Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fernando R. Fernandez ◽  
Mircea C. Iftinca ◽  
Gerald W. Zamponi ◽  
Ray W. Turner
Keyword(s):  
Calcium Channel ◽  
Neuronal Excitability ◽  
Neuronal Firing ◽  
Mammalian Brain ◽  
Peripheral Tissues ◽  
Window Current ◽  
Modeling Data ◽  
The Brain ◽  
Firing Neuron ◽  
Cav3 Channel

AbstractT-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

scholarly journals Interphotoreceptor coupling: an evolutionary perspective

2021 ◽  
Author(s):  
Lorenzo Cangiano ◽  
Sabrina Asteriti
Keyword(s):  
Visual Information ◽  
Signal To Noise Ratio ◽  
Electrical Coupling ◽  
Physiological Role ◽  
Cellular Processes ◽  
Contact Points ◽  
Highly Sensitive ◽  
The Many ◽  
The Impact

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.

Activation of Protein Kinase C Increases Neuronal Excitability by Regulating Persistent Na+ Current in Mouse Neocortical Slices

1998 ◽  
Vol 80 (3) ◽  
pp. 1547-1551 ◽  
Author(s):  
Nadav Astman ◽  
Michael J. Gutnick ◽  
Ilya A. Fleidervish
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potential ◽  
Neuronal Excitability ◽  
Specific Protein ◽  
Protein Kinase C Inhibitors ◽  
Cationic Current ◽  
Kinase C ◽  
Layer V ◽  
Neuronal Functions

Astman, Nadav, Michael J. Gutnick, and Ilya A. Fleidervish. Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices. J. Neurophysiol. 80: 1547–1551, 1998. Effects of the protein kinase C activating phorbol ester, phorbol 12-myristate 13-acetate (PMA), were studied in whole cell recordings from layer V neurons in slices of mouse somatosensory neocortex. PMA was applied intracellularly (100 nM to 1 μM) to restrict its action to the cell under study. In current-clamp recordings, it enhanced neuronal excitability by inducing a 10- to 20-mV decrease in voltage threshold for action-potential generation. Because spike threshold in neocortical neurons critically depends on the properties of persistent Na+ current ( I NaP), effects of PMA on this current were studied in voltage clamp. After blocking K+ and Ca2+ currents, I NaP was revealed by applying slow depolarizing voltage ramps from −70 to 0 mV. Intracellular PMA induced a decrease in I NaP at very depolarized membrane potentials. It also shifted activation of I NaP in the hyperpolarizing direction, however, such that there was a significant increase in persistent inward current at potentials more negative than −45 mV. When tetrodotoxin (TTX) was added to the bath, blocking I NaP and leaving only an outward nonspecific cationic current ( I cat), PMA had no apparent effect on responses to voltage ramps. Thus PMA did not affect I cat, and it did not induce any additional current. Intracellular application of the inactive PMA analogue, 4α-PMA, did not affect I NaP. The specific protein kinase C inhibitors, chelerythrine (20 μM) and calphostin C (10 μM), blocked the effect of PMA on I NaP. The data suggest that PMA enhances neuronal excitability via a protein kinase C–mediated increase in I NaP at functionally critical subthreshold voltages. This novel effect would modulate all neuronal functions that are influenced by I NaP, including synaptic integration and active backpropagation of action potential from the soma into the dendrites.

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