scholarly journals K v 3.1/K v 3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons

2017 ◽  
Vol 118 ◽  
pp. 102-112 ◽  
Author(s):  
Kim Boddum ◽  
Charlotte Hougaard ◽  
Julie Xiao-Ying Lin ◽  
Nadia Lybøl von Schoubye ◽  
Henrik Sindal Jensen ◽  
...  
2017 ◽  
Vol 108 ◽  
pp. 100-114 ◽  
Author(s):  
Feng Gu ◽  
Isabel Parada ◽  
Fran Shen ◽  
Judith Li ◽  
Alberto Bacci ◽  
...  

2017 ◽  
Vol 117 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Kévin Marche ◽  
Paul Apicella

Recent works highlight the importance of local inhibitory interneurons in regulating the function of the striatum. In particular, fast-spiking interneurons (FSIs), which likely correspond to a subgroup of GABAergic interneurons, have been involved in the control of movement by exerting strong inhibition on striatal output pathways. However, little is known about the exact contribution of these presumed interneurons in movement preparation, initiation, and execution. We recorded the activity of FSIs in the striatum of monkeys as they performed reaching movements to a visual target under two task conditions: one in which the movement target was presented at unsignaled left or right locations, and another in which advance information about target location was available, thus allowing monkeys to react faster. Modulations of FSI activity around the initiation of movement (53% of 55 neurons) consisted mostly of increases reaching maximal firing immediately before or, less frequently, after movement onset. Another subset of FSIs showed decreases in activity during movement execution. Rarely did movement-related changes in FSI firing depend on response direction and movement speed. Modulations of FSI activity occurring relatively early in relation to movement initiation were more influenced by the preparation for movement, compared with those occurring later. Conversely, FSI activity remained unaffected, as monkeys were preparing a movement toward a specific location and instead moved to the opposite direction when the trigger occurred. These results provide evidence that changes in activity of presumed GABAergic interneurons of the primate striatum could make distinct contributions to processes involved in movement generation. NEW & NOTEWORTHY We explored the functional contributions of striatal fast-spiking interneurons (FSIs), presumed GABAergic interneurons, to distinct steps of movement generation in monkeys performing a reaching task. The activity of individual FSIs was modulated before and during the movement, consisting mostly of increased in firing rates. Changes in activity also occurred during movement preparation. We interpret this variety of modulation types at different moments of task performance as reflecting differential FSI control over distinct phases of movement.


2021 ◽  
Vol 118 (51) ◽  
pp. e2114549118
Author(s):  
Ricardo Martins Merino ◽  
Carolina Leon-Pinzon ◽  
Walter Stühmer ◽  
Martin Möck ◽  
Jochen F. Staiger ◽  
...  

Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity of different GABAergic interneurons in prefrontal cortex under conditions mimicking distinct brain states. While fast-spiking neurons always exhibited a wide bandwidth of around 400 Hz, the response properties of spike-frequency adapting interneurons switched with the background input’s statistics. Slowly fluctuating background activity, as typical for sleep or quiet wakefulness, dramatically boosted the neurons’ sensitivity to gamma and ripple frequencies. We developed a time-resolved dynamic gain analysis and revealed rapid sensitivity modulations that enable neurons to periodically boost gamma oscillations and ripples during specific phases of ongoing low-frequency oscillations. This mechanism predicts these prefrontal interneurons to be exquisitely sensitive to high-frequency ripples, especially during brain states characterized by slow rhythms, and to contribute substantially to theta-gamma cross-frequency coupling.


2002 ◽  
Vol 87 (4) ◽  
pp. 2190-2194 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).


Author(s):  
Bo Wang ◽  
Wei Ke ◽  
Jing Guang ◽  
Guang Chen ◽  
Luping Yin ◽  
...  

2005 ◽  
Vol 22 (5) ◽  
pp. 1097-1108 ◽  
Author(s):  
Joshua L. Plotkin ◽  
Nanping Wu ◽  
Marie-Françoise Chesselet ◽  
Michael S. Levine

2011 ◽  
Vol 106 (2) ◽  
pp. 775-787 ◽  
Author(s):  
Matthew S. Lazarus ◽  
Z. Josh Huang

In the rodent primary visual cortex, maturation of GABA inhibitory circuitry is regulated by visual input and contributes to the onset and progression of ocular dominance (OD) plasticity. Cortical inhibitory circuitry consists of diverse groups of GABAergic interneurons, which display distinct physiological properties and connectivity patterns. Whether different classes of interneurons mature with similar or distinct trajectories and how their maturation profiles relate to experience dependent development are not well understood. We used green fluorescent protein reporter lines to study the maturation of two broad classes of cortical interneurons: parvalbumin-expressing (PV) cells, which are fast spiking and innervate the soma and proximal dendrites, and somatostatin-expressing (SOM) cells, which are regular spiking and target more distal dendrites. Both cell types demonstrate extensive physiological maturation, but with distinct trajectories, from eye opening to the peak of OD plasticity. Typical fast-spiking characteristics of PV cells became enhanced, and synaptic signaling from PV to pyramidal neurons became faster. SOM cells demonstrated a large increase in input resistance and a depolarization of resting membrane potential, resulting in increased excitability. While the substantial maturation of PV cells is consistent with the importance of this source of inhibition in triggering OD plasticity, the significant increase in SOM cell excitability suggests that dendrite-targeted inhibition may also play a role in OD plasticity. More generally, these results underscore the necessity of cell type-based analysis and demonstrate that distinct classes of cortical interneurons have markedly different developmental profiles, which may contribute to the progressive emergence of distinct functional properties of cortical circuits.


1999 ◽  
Vol 82 (5) ◽  
pp. 2476-2489 ◽  
Author(s):  
A. Erisir ◽  
D. Lau ◽  
B. Rudy ◽  
C. S. Leonard

Fast-spiking GABAergic interneurons of the neocortex and hippocampus fire high-frequency trains of brief action potentials with little spike-frequency adaptation. How these striking properties arise is unclear, although recent evidence suggests K+ channels containing Kv3.1-Kv3.2 proteins play an important role. We investigated the role of these channels in the firing properties of fast-spiking neocortical interneurons from mouse somatosensory cortex using a pharmacological and modeling approach. Low tetraethylammonium (TEA) concentrations (≤1 mM), which block only a few known K+channels including Kv3.1-Kv3.2, profoundly impaired action potential repolarization and high-frequency firing. Analysis of the spike trains evoked by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca2+-activated K+ channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3.2–like current in fast-spiking neurons, but not in other interneurons. Analysis of spike shape changes during the spike trains suggested that Na+ channel inactivation plays a significant role in the firing-rate slowdown produced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enable sustained high-frequency firing by facilitating the recovery of Na+ channel inactivation and by minimizing the duration of the afterhyperpolarization in neocortical interneurons.


2002 ◽  
Vol 87 (3) ◽  
pp. 1303-1310 ◽  
Author(s):  
Darrell M. Porcello ◽  
Chi Shun Ho ◽  
Rolf H. Joho ◽  
John R. Huguenard

Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K+ channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23°C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1−/−) compared with their wild-type (Kv3.1+/+) counterparts had reduced amplitudes (−6%) and fast after-hyperpolarizations (−16%). At 34°C, action potentials in Kv3.1−/− mice had increased duration (21%) due to a reduced rate of repolarization (−30%) when compared with wild-type controls. Action potential trains in Kv3.1−/− were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship ( F/I) at 34°C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca2+ bursts in Kv3.1−/− RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.


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