scholarly journals GABABR Modulation of Electrical Synapses and Plasticity in the Thalamic Reticular Nucleus

2021 ◽  
Vol 22 (22) ◽  
pp. 12138
Author(s):  
Huaixing Wang ◽  
Julie S. Haas
Keyword(s):  
Signaling Pathways ◽  
Neuronal Activity ◽  
Gabab Receptor ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Electrical Synapse ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Electrical Synapses ◽  
The Impact

Two distinct types of neuronal activity result in long-term depression (LTD) of electrical synapses, with overlapping biochemical intracellular signaling pathways that link activity to synaptic strength, in electrically coupled neurons of the thalamic reticular nucleus (TRN). Because components of both signaling pathways can also be modulated by GABAB receptor activity, here we examined the impact of GABAB receptor activation on the two established inductors of LTD in electrical synapses. Recording from patched pairs of coupled rat neurons in vitro, we show that GABAB receptor inactivation itself induces a modest depression of electrical synapses and occludes LTD induction by either paired bursting or metabotropic glutamate receptor (mGluR) activation. GABAB activation also occludes LTD from either paired bursting or mGluR activation. Together, these results indicate that afferent sources of GABA, such as those from the forebrain or substantia nigra to the reticular nucleus, gate the induction of LTD from either neuronal activity or afferent glutamatergic receptor activation. These results add to a growing body of evidence that the regulation of thalamocortical transmission and sensory attention by TRN is modulated and controlled by other brain regions. Significance: We show that electrical synapse plasticity is gated by GABAB receptors in the thalamic reticular nucleus. This effect is a novel way for afferent GABAergic input from the basal ganglia to modulate thalamocortical relay and is a possible mediator of intra-TRN inhibitory effects.

scholarly journals Activity-dependent long-term potentiation of electrical synapses in the mammalian thalamus

2019 ◽  
Author(s):  
Brandon Fricker ◽  
Emily Heckman ◽  
Patrick C. Cunningham ◽  
Julie S. Haas
Keyword(s):  
Brain Area ◽  
Long Term Potentiation ◽  
Electrical Synapse ◽  
Thalamic Reticular Nucleus ◽  
Calcium Flux ◽  
Reticular Nucleus ◽  
Electrical Synapses ◽  
Term Potentiation ◽  
Activity Dependent

AbstractActivity-dependent changes of synapse strength have been extensively characterized at chemical synapses, but the relationship between physiological forms of activity and strength at electrical synapses remains poorly understood. For mammalian electrical synapses composed of hexomers of connexin36, physiological forms of neuronal activity in coupled pairs has thus far have only been linked to long-term depression; activity that results in strengthening of electrical synapses has not yet been identified. The thalamic reticular nucleus (TRN), a central brain area primarily connected by gap junctional (electrical) synapses, regulates cortical attention to the sensory surround. Bidirectional plasticity of electrical synapses may be a key mechanism underlying these processes in both healthy and diseased states. Here we show in electrically coupled TRN pairs that tonic spiking in one neuron results in long-term potentiation of electrical synapses between coupled pairs of TRN neurons. Potentiation is expressed asymmetrically, indicating that regulation of connectivity depends on the direction of use. Further, potentiation depends on calcium flux, and we thus propose a calcium-based activity rule for bidirectional plasticity of electrical synapse strength. Because electrical synapses dominate intra-TRN connectivity, these synapses and their modifications are key regulators of thalamic attention circuitry. More broadly, bidirectional modifications of electrical synapses are likely to be a widespread and powerful principle for ongoing, dynamic reorganization of neuronal circuitry across the brain.SummaryLong-term potentiation results from spiking in one cell of an electrically coupled pair. Asymmetry of synapses increases following unidirectional activity. We suggest a calcium-based rule for electrical synapse plasticity.

scholarly journals Activity-dependent long-term potentiation of electrical synapses in the mammalian thalamus

2020 ◽  
Author(s):  
Brandon Alexander Fricker ◽  
Emily Lauren Heckman ◽  
Patrick C Cunningham ◽  
Huaixing Wang ◽  
Julie S Haas
Keyword(s):  
Brain Area ◽  
Long Term Potentiation ◽  
Electrical Synapse ◽  
Thalamic Reticular Nucleus ◽  
Calcium Flux ◽  
Reticular Nucleus ◽  
Electrical Synapses ◽  
Term Potentiation ◽  
Activity Dependent

Activity-dependent changes of synapse strength have been extensively characterized at chemical synapses, but the relationship between physiological forms of activity and strength at electrical synapses remains poorly characterized and understood. For mammalian electrical synapses comprising hexamers of connexin36, physiological forms of neuronal activity in coupled pairs have thus far only been linked to long-term depression; activity that results in strengthening of electrical synapses has not yet been identified. The thalamic reticular nucleus (TRN), a central brain area primarily interconnected by electrical synapses, regulates cortical input from and attention to the sensory surround. Here, we show in electrically coupled TRN pairs that tonic spiking in one neuron results in long-term potentiation of electrical synapses with a magnitude of plasticity that alters the functionality of the synapse. Potentiation is expressed asymmetrically, indicating that regulation of connectivity depends on the direction of use. Further, potentiation depends on calcium flux, and we thus propose a calcium-based activity rule for bidirectional plasticity of electrical synapse strength. Because electrical synapses dominate intra-TRN connectivity, these synapses and their activity-dependent modifications are key dynamic regulators of thalamic attention circuitry. More broadly, we speculate that bidirectional modifications of electrical synapses may be a widespread and powerful principle for ongoing, dynamic reorganization of neuronal circuitry across the brain.

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.

Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1993-2003 ◽  
Author(s):  
R. A. Warren ◽  
A. Agmon ◽  
E. G. Jones
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Initial Response ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Excitatory Postsynaptic Potential ◽  
Postsynaptic Potential ◽  
Synaptic Interactions ◽  
Gabaa Receptor Antagonist

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.

scholarly journals A novel mutual information estimator to measure spike train correlations in a model thalamocortical network

2018 ◽  
Vol 120 (6) ◽  
pp. 2730-2744 ◽  
Author(s):  
Ekaterina D. Gribkova ◽  
Baher A. Ibrahim ◽  
Daniel A. Llano
Keyword(s):  
Mutual Information ◽  
Information Transmission ◽  
Spike Train ◽  
Calcium Current ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Sensory Signals ◽  
Layer 4 ◽  
The Impact ◽  
Current Conductance

The impact of thalamic state on information transmission to the cortex remains poorly understood. This limitation exists due to the rich dynamics displayed by thalamocortical networks and because of inadequate tools to characterize those dynamics. Here, we introduce a novel estimator of mutual information and use it to determine the impact of a computational model of thalamic state on information transmission. Using several criteria, this novel estimator, which uses an adaptive partition, is shown to be superior to other mutual information estimators with uniform partitions when used to analyze simulated spike train data with different mean spike rates, as well as electrophysiological data from simultaneously recorded neurons. When applied to a thalamocortical model, the estimator revealed that thalamocortical cell T-type calcium current conductance influences mutual information between the input and output from this network. In particular, a T-type calcium current conductance of ~40 nS appears to produce maximal mutual information between the input to this network (conceptualized as afferent input to the thalamocortical cell) and the output of the network at the level of a layer 4 cortical neuron. Furthermore, at particular combinations of inputs to thalamocortical and thalamic reticular nucleus cells, thalamic cell bursting correlated strongly with recovery of mutual information between thalamic afferents and layer 4 neurons. These studies suggest that the novel mutual information estimator has advantages over previous estimators and that thalamic reticular nucleus activity can enhance mutual information between thalamic afferents and thalamorecipient cells in the cortex. NEW & NOTEWORTHY In this study, a novel mutual information estimator was developed to analyze information flow in a model thalamocortical network. Our findings suggest that this estimator is a suitable tool for signal transmission analysis, particularly in neural circuits with disparate firing rates, and that the thalamic reticular nucleus can potentiate ascending sensory signals, while thalamic recipient cells in the cortex can recover mutual information in ascending sensory signals that is lost due to thalamic bursting.

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

Characterizing rare mis-sense variations of CACNA1I identified in a Swedish schizophrenia cohort

2016 ◽  
Vol 33 (S1) ◽  
pp. S182-S183
Author(s):  
J. Pan ◽  
A. Allen ◽  
L. huang ◽  
D. Daez
Keyword(s):  
Calcium Influx ◽  
Association Studies ◽  
Expression System ◽  
Single Copy ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Patient Specific ◽  
Genome Wide Association Studies ◽  
The Impact

CACNA1I (hCaV3.3) encodes the α1 pore-forming subunit of human voltage-gated T-type calcium channels. CaV3.3 is expressed in a limited subset of neurons including GABAergic neurons of the thalamic reticular nucleus (TRN) where they support oscillatory activity essential for sleep spindle generation. CACNA1I is implicated in schizophrenia risk by emerging genetics including genome-wide association studies (PGC, 2014), and exome sequencing of trio samples (Gulsuner et al., 2013). In order to understand the impact of disease-associated sequence variation on the function of CaV3.3, we set out to analyze a complete set of rare mis-sense coding variations in CACNA1I in a Swedish cohort, including 15 variations identified in patients, 20 identified in control subjects, and 23 in both. We established a heterologous expression system of isogenic cell lines, each carrying single-copy inducible cDNA variants of hCaV3.3, and evaluated their functional impact on channel function by electrophysiology, calcium imaging, and biochemistry. We found at least five coding variations impaired overall channel protein abundance, as well as whole cell current density. In addition, we identified hCaV3.3 variants with altered voltage-dependence of channel activation and inactivation. Overall, we found that reduced calcium influx through hCaV3.3 is associated with the group of variants identified in patients, compared to those in both patients and controls. Our findings suggest that patient-specific rare variations of CACNA1I may influence channel-dependent functions, including rebound bursting in TRN neurons, with potential implications for schizophrenia pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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