scholarly journals Somatic and dendritic GABAB receptors regulate neuronal excitability via different mechanisms

2012 ◽  
Vol 108 (10) ◽  
pp. 2810-2818 ◽  
Author(s):  
Jean-Didier Breton ◽  
Greg J. Stuart
Keyword(s):  
Potassium Channels ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Membrane Properties ◽  
Dendritic Excitability ◽  
The Impact ◽  
Neuronal Output

GABAB receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABAB receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABAB receptors. Here, we investigate the impact of GABAB receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABAB receptors led to hyperpolarization and a decrease in membrane resistance that was greatest at somatic and proximal dendritic locations. These effects were occluded by low concentrations of barium (100 μM), suggesting that they are mediated by potassium channels. In contrast, activation of dendritic GABAB receptors decreased the width of backpropagating action potential (APs) and abolished dendritic calcium electrogenesis, indicating that dendritic GABAB receptors regulate excitability, primarily via inhibition of voltage-dependent calcium channels. These distinct actions of somatic and dendritic GABAB receptors regulated neuronal output in different ways. Activation of somatic GABAB receptors led to a reduction in neuronal output, primarily by increasing the AP rheobase, whereas activation of dendritic GABAB receptors blocked burst firing, decreasing AP output in the absence of a significant change in somatic membrane properties. Taken together, our results show that GABAB receptors regulate somatic and dendritic excitability of cortical pyramidal neurons via different cellular mechanisms. Somatic GABAB receptors activate potassium channels, leading primarily to a subtractive or shunting form of inhibition, whereas dendritic GABAB receptors inhibit dendritic calcium electrogenesis, leading to a reduction in bursting firing.

scholarly journals Potassium channels contribute to activity-dependent scaling of dendritic inhibition

2017 ◽  
Author(s):  
Jeremy T. Chang ◽  
Michael J. Higley
Keyword(s):  
Potassium Channels ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Gabaergic Inhibition ◽  
Voltage Gated ◽  
The Impact ◽  
Activity Dependent

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.

Development of Intrinsic Properties and Excitability of Layer 2/3 Pyramidal Neurons During a Critical Period for Sensory Maps in Rat Barrel Cortex

2004 ◽  
Vol 92 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Miguel Maravall ◽  
Edward A. Stern ◽  
Karel Svoboda
Keyword(s):  
Critical Period ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Sensory Maps ◽  
Layer 2 ◽  
Whole Cell Recordings ◽  
Passive Membrane Properties

The development of layer 2/3 sensory maps in rat barrel cortex (BC) is experience dependent with a critical period around postnatal days (PND) 10–14. The role of intrinsic response properties of neurons in this plasticity has not been investigated. Here we characterize the development of BC layer 2/3 intrinsic responses to identify possible sites of plasticity. Whole cell recordings were performed on pyramidal cells in acute BC slices from control and deprived rats, over ages spanning the critical period (PND 12, 14, and 17). Vibrissa trimming began at PND 9. Spiking behavior changed from phasic (more spike frequency adaptation) to regular (less adaptation) with age, such that the number of action potentials per stimulus increased. Changes in spiking properties were related to the strength of a slow Ca2+-dependent afterhyperpolarization. Maturation of the spiking properties of layer 2/3 pyramidal neurons coincided with the close of the critical period and was delayed by deprivation. Other measures of excitability, including I-f curves and passive membrane properties, were affected by development but unaffected by whisker deprivation.

scholarly journals Impact of inhibitory constraint of interneurons on neuronal excitability

2013 ◽  
Vol 110 (11) ◽  
pp. 2520-2535 ◽  
Author(s):  
Vallent Lee ◽  
Jamie Maguire
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Molecular Layer ◽  
Critical Role ◽  
Tonic Inhibition ◽  
Stratum Radiatum ◽  
Gabaergic Inhibition ◽  
Seizure Susceptibility ◽  
Ca1 Pyramidal Neurons ◽  
The Impact

Tonic inhibition is thought to dampen the excitability of principal neurons; however, little is known about the role of tonic GABAergic inhibition in interneurons and the impact on principal neuron excitability. In many brain regions, tonic GABAergic inhibition is mediated by extrasynaptic, δ-subunit-containing GABAA receptors (GABAARs). In the present study we demonstrate the importance of GABAAR δ-subunit-mediated tonic inhibition in interneurons. Selective elimination of the GABAAR δ-subunit from interneurons was achieved by crossing a novel floxed Gabrd mouse model with GAD65-Cre mice ( Gabrd/Gad mice). Deficits in GABAAR δ-subunit expression in GAD65-positive neurons result in a decrease in tonic GABAergic inhibition and increased excitability of both molecular layer (ML) and stratum radiatum (SR) interneurons. Disinhibition of interneurons results in robust alterations in the neuronal excitability of principal neurons and decreased seizure susceptibility. Gabrd/Gad mice have enhanced tonic and phasic GABAergic inhibition in both CA1 pyramidal neurons and dentate gyrus granule cells (DGGCs). Consistent with alterations in hippocampal excitability, CA1 pyramidal neurons and DGGCs from Gabrd/Gad mice exhibit a shift in the input-output relationship toward decreased excitability compared with those from Cre−/− littermates. Furthermore, seizure susceptibility, in response to 20 mg/kg kainic acid, is significantly decreased in Gabrd/Gad mice compared with Cre−/− controls. These data demonstrate a critical role for GABAAR δ-subunit-mediated tonic GABAergic inhibition of interneurons on principal neuronal excitability and seizure susceptibility.

scholarly journals Active dendrites, potassium channels and synaptic plasticity

2003 ◽  
Vol 358 (1432) ◽  
pp. 667-674 ◽  
Author(s):  
Daniel Johnston ◽  
Brian R. Christie ◽  
Andreas Frick ◽  
Richard Gray ◽  
Dax A. Hoffman ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Pyramidal Neurons ◽  
Back Propagation ◽  
Dendritic Tree ◽  
Long Term Potentiation ◽  
Synaptic Potentials ◽  
Dendritic Excitability

The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons.

Muscarinic Receptor Activation Induces Depolarizing Plateau Potentials in Bursting Neurons of the Rat Subiculum

1999 ◽  
Vol 82 (5) ◽  
pp. 2590-2601 ◽  
Author(s):  
Hiroto Kawasaki ◽  
Carmela Palmieri ◽  
Massimo Avoli
Keyword(s):  
Neuronal Excitability ◽  
Excitatory Amino Acid ◽  
Receptor Activation ◽  
Membrane Properties ◽  
Mammalian Brain ◽  
Resting Membrane Potential ◽  
Limbic Structure ◽  
Plateau Potentials ◽  
Cortical Cells ◽  
Fire Action Potential

Acetylcholine functions as a neuromodulator in the mammalian brain by binding to specific receptors and thus bringing about profound changes in neuronal excitability. Activation of muscarinic receptors often results in an increased excitability of cortical cells. It is, however, unknown whether such an action is present in the subiculum, a limbic structure that may be involved in cognitive processes as well as in seizure propagation. Most rat subicular neurons are endowed of intrinsic membrane properties that make them fire action potential bursts. Using intracellular recordings from these bursting cells in a slice preparation, we report here that application of the cholinergic agonist carbachol (CCh, 30–100 μM) to medium containing ionotropic excitatory amino acid receptor antagonists reduces burst-afterhyperpolarizations (burst-AHPs) and discloses depolarizing plateau potentials that outlast the triggering current pulses by 140–2,800 ms. These plateau potentials appear with CCh concentrations >50 μM and are dependent on the resting membrane potential and on the intensity/duration of the triggering pulse; are recorded during application of tetrodotoxin (1 μM, n = 5 neurons); but are markedly reduced by replacing 82% of extracellular Na+with equimolar choline ( n = 6). Plateau potentials also are abolished by Co2+ (2 mM; n = 5) or Cd2+ (1 mM; n = 2) application and by recording with electrodes containing the Ca2+chelator bis(2-aminophenoxy)ethane- N, N,N′,N′-tetraacetic acid (0.2 M; n = 6). CCh-induced burst-AHP reduction and plateau potentials are reversed by the muscarinic antagonist atropine (0.5 μM, n = 7). In conclusion, our findings demonstrate a powerful muscarinic modulation of the intrinsic excitability of subicular bursting cells that is predominated by the appearance of plateau potentials. These changes in excitability may contribute to physiological processes such as learning or memory and play a role in the generation of epileptiform depolarizations. We propose that, as in other limbic structures, muscarinic plateau potentials in the subiculum are mainly due to a Ca2+-dependent nonselective cationic conductance.

Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor

2012 ◽  
Vol 108 (5) ◽  
pp. 1521-1528 ◽  
Author(s):  
Luuk van der Velden ◽  
Johannes A. van Hooft ◽  
Pascal Chameau
Keyword(s):  
Firing Pattern ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Dendritic Morphology ◽  
Neuronal Firing ◽  
Specific Class ◽  
Postnatal Maturation ◽  
Layer 2 ◽  
The Impact ◽  
Dendritic Complexity

We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT3 receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT3A receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT3A knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.

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 Μελέτη της διεγερσιμότητας των πυραμιδοειδών νευρώνων της περιοχής CA1 του ιπποκάμπου

2003 ◽  
Author(s):  
Γκρέτα Βόζνιακ
Keyword(s):  
Current Pulse ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Input Resistance ◽  
Longitudinal Axis ◽  
Functional Differentiation ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Firing Characteristics

Recent reports have acknowledged the existence of functional differentiation along the longitudinal axis of the hippocampus, the ventral part being more prone to epileptogenesis. The aim of the present study was to investigate the membrane properties and firing characteristics of principal neurons of dorsal (DH) and ventral hippocampus (VH) that might account for this differentiation. Intracellular recordings were made from CA1 pyramidal neurons of DH and VH hippocampus. Resting membrane potential (DH: -64,17±0,65mV; VH: -63,84±0,82mV), input resistance (DH: 45,92±4,99ΜΩ; VH: 46,28±6,24ΜΩ), and time constant (DH: 22,11 ±1,13ms; VH: 19,32±0,87ms) did not differ between DH (n=21 and VH (n=12) neurons. Action potential (AP) parameters were measured from single AP's elicited by brief current pulse (3-1 Oms) in DH (n=7) and VH (n=7) neurons. Peak amplitude (DH: 89,71±1,99mV; VH: 80,57±1,92 mV), rise time (DH: 0,22±0,01ms; VH: 0,21±0,01ms), decay time (DH: 0,97±0,02ms: VH: 0,98±0,02ms), half width (DH: 1,31±0,07ms; VH: 1,14 ±0,03ms). However, fast afterhyperpolarizations (fAHP) following AP’s were significantly weaker in VH (-4,07±0,7mV) compared to DH (-7,53±1,16mV) neurons (p<0,05). Moreover, the 1st interspike interval (ISI; DH: 4,9±0,34ms, n=25; VH: 3,9±0,3ms, n=15) of a train of AP’s elicited by a depolarizing current pulse (500ms, 0.4nA), as well as the number of AP’s within the pulse (DH: 6,8±0,9; VH: 12,1 ±0,2), was significantly different between the two groups of neurons (p<0,05). The data suggest that the weaker fAHP in VH could underlie its higher neuronal excitability as expressed by the shorter ISI. These finding confirm and extend previous evidence for functional differentiation between DH and VH and explain, to some extend, the relatively higher tendency of VH toward epileptiform activity.

scholarly journals Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Scott L Jones ◽  
Minh-Son To ◽  
Greg J Stuart
Keyword(s):  
Synaptic Plasticity ◽  
Potassium Channels ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Spike Timing ◽  
Sk Channels ◽  
Sk Channel ◽  
Calcium Activated Potassium Channels ◽  
Small Conductance

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

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