scholarly journals Serotonin enhances excitability and gamma frequency temporal integration in mouse prefrontal fast-spiking interneurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jegath C Athilingam ◽  
Roy Ben-Shalom ◽  
Caroline M Keeshen ◽  
Vikaas S Sohal ◽  
Kevin J Bender

The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30–100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs. This leads to depolarization, increased input resistance, enhanced spiking, and slowed decay of excitatory post-synaptic potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially enhanced temporal summation and firing elicited by gamma frequency inputs. These findings show how changes in passive membrane properties can affect not only neuronal excitability but also the temporal filtering of synaptic inputs.

1969 ◽  
Vol 53 (3) ◽  
pp. 279-297 ◽  
Author(s):  
Robert S. Eisenberg ◽  
Peter W. Gage

The resting ionic conductances of frog sartorius muscle fibers have been determined in a variety of conditions in order to measure the potassium conductance of the tubular and surface membranes (gKt and gKs) and the chloride conductance of the tubular and surface membranes (gClt and gCls). In both normal fibers and fibers without tubules, measurements of input resistance and diameter were made at normal pH and at low pH when the chloride conductance was very small. These measurements permitted the separation of the ionic conductances: gCls = 219 µmhos/cm2; gClt = 0 µmhos/cm2; gKs = 28 µmhos/cm2; gKt = 55 µmhos/cm2. Possible sources of systematic error are discussed and a statistical analysis of the effects of random error is presented. The implications of the nonuniformity of membrane properties are discussed along with possible anatomical explanations.


2017 ◽  
Author(s):  
Jegath C Athilingam ◽  
Roy Ben-Shalom ◽  
Caroline M Keeshen ◽  
Vikaas S Sohal ◽  
Kevin J Bender

2003 ◽  
Author(s):  
Γκρέτα Βόζνιακ

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.


1987 ◽  
Vol 57 (3) ◽  
pp. 633-644 ◽  
Author(s):  
S. J. Redman ◽  
E. M. McLachlan ◽  
G. D. Hirst

We have studied the passive membrane properties of sympathetic neurons in isolated lumbar paravertebral ganglia of young rats by recording the voltage response to small steps of current passed through an intracellular microelectrode. Substitution of Ba2+ (2.5 mM) for Ca2+ (2.5 mM) in the bathing solution increased the input resistance and the time constant of the voltage response, but the increase in time constant was disproportionately large relative to the increase in input resistance. After consideration of the passive electrical properties and the geometry of the soma and dendrites, it was concluded that the disproportionate change in input resistance and time constant could be explained if barium inactivated a resting potassium conductance that was concentrated in the distal dendrites. In the APPENDIX, the effect of nonuniform membrane conductance on the relationship between input resistance and time constant in models of these neurons is analyzed.


2009 ◽  
Vol 102 (6) ◽  
pp. 3365-3383 ◽  
Author(s):  
Yue Dai ◽  
Kevin P. Carlin ◽  
Zongming Li ◽  
Douglas G. McMahon ◽  
Robert M. Brownstone ◽  
...  

Although locomotion is known to be generated by networks of spinal neurons, knowledge of the properties of these neurons is limited. Using neonatal transgenic mice that express enhanced green fluorescent protein (EGFP) driven by the c-fos promoter, we visualized EGFP-positive neurons in spinal cord slices from animals that were subjected to a locomotor task or drug cocktail [ N-methyl-d-aspartate, serotonin (5-HT), dopamine, and acetylcholine (ACh)]. The activity-dependent expression of EGFP was also induced in dorsal root ganglion neurons with electrical stimulation of the neurons. Following 60–90 min of swimming, whole cell patch-clamp recordings were made from EGFP+ neurons in laminae VII, VIII, and X from slices of segments T12 to L4. The EGFP+ neurons ( n = 55) could be classified into three types based on their responses to depolarizing step currents: single spike, phasic firing, and tonic firing. Membrane properties observed in these neurons include hyperpolarization-activated inward currents (29/55), postinhibitory rebound (11/55), and persistent-inward currents (31/55). Bath application of 10–40 μM 5-HT and/or ACh increased neuronal excitability or output with hyperpolarization of voltage threshold and changes in membrane potential. 5-HT also increased input resistance, reduced the afterhyperpolarization (AHP), and induced membrane oscillations, whereas ACh reduced the input resistance and increased the AHP. In this study, we demonstrate a new way of identifying neurons active in locomotion. Our results suggest that the EGFP+ neurons are a heterogeneous population of interneurons. The actions of 5-HT and ACh on these neurons provide insights into the neuronal properties modulated by these transmitters for generation of locomotion.


2021 ◽  
Vol 14 (6) ◽  
pp. 519
Author(s):  
Sion Park ◽  
Pia Flüthmann ◽  
Carla Wolany ◽  
Lena Goedecke ◽  
Hannah Maleen Spenner ◽  
...  

Background: The neuropeptide S system, consisting of the 20 amino acid neuropeptide NPS and its G-protein-coupled receptor (GPCR) neuropeptide S receptor 1 (NPSR1), has been studied intensively in rodents. Although there is a lot of data retrieved from behavioral studies using pharmacology or genetic interventions, little is known about intracellular signaling cascades in neurons endogenously expressing the NPSR1. Methods: To elucidate possible G-protein-dependent signaling and effector systems, we performed whole-cell patch-clamp recordings on principal neurons of the anterior basolateral amygdala of mice. We used pharmacological interventions to characterize the NPSR1-mediated current induced by NPS application. Results: Application of NPS reliably evokes inward-directed currents in amygdalar neurons recorded in brain slice preparations of male and female mice. The NPSR1-mediated current had a reversal potential near the potassium reversal potential (EK) and was accompanied by an increase in membrane input resistance. GDP-β-S and BAPTA, but neither adenylyl cyclase inhibition nor 8-Br-cAMP, abolished the current. Intracellular tetraethylammonium or 4-aminopyridine reduced the NPS-evoked current. Conclusion: NPSR1 activation in amygdalar neurons inhibits voltage-gated potassium (K+) channels, most likely members of the delayed rectifier family. Intracellularly, Gαq signaling and calcium ions seem to be mandatory for the observed current and increased neuronal excitability.


1985 ◽  
Vol 54 (2) ◽  
pp. 245-260 ◽  
Author(s):  
C. E. Stansfeld ◽  
D. I. Wallis

The active and passive membrane properties of rabbit nodose ganglion cells and their responsiveness to depolarizing agents have been examined in vitro. Neurons with an axonal conduction velocity of less than 3 m/s were classified as C-cells and the remainder as A-cells. Mean axonal conduction velocities of A- and C-cells were 16.4 m/s and 0.99 m/s, respectively. A-cells had action potentials of brief duration (1.16 ms), high rate of rise (385 V/s), an overshoot of 23 mV, and relatively high spike following frequency (SFF). C-cells typically had action potentials with a "humped" configuration (duration 2.51 ms), lower rate of rise (255 V/s), an overshoot of 28.6 mV, an after potential of longer duration than A-cells, and relatively low SFF. Eight of 15 A-cells whose axons conducted at less than 10 m/s had action potentials of longer duration with a humped configuration; these were termed Ah-cells. They formed about 10% of cells whose axons conducted above 2.5 m/s. The soma action potential of A-cells was blocked by tetrodotoxin (TTX), but that of 6/11 C-cells was unaffected by TTX. Typically, A-cells showed strong delayed (outward) rectification on passage of depolarizing current through the soma membrane and time-dependent (inward) rectification on inward current passage. Input resistance was thus highly sensitive to membrane potential close to rest. In C-cells, delayed rectification was not marked, and slight time-dependent rectification occurred in only 3 of 25 cells; I/V curves were normally linear over the range: resting potential to 40 mV more negative. Data on Ah-cells were incomplete, but in our sample of eight cells time-dependent rectification was absent or mild. C-cells had a higher input resistance and a higher neuronal capacitance than A-cells. In a proportion of A-cells, RN was low at resting potential (5 M omega) but increased as the membrane was hyperpolarized by a few millivolts. A-cells were depolarized by GABA but were normally unaffected by 5-HT or DMPP. C-cells were depolarized by GABA in a similar manner to A-cells but also responded strongly to 5-HT; 53/66 gave a depolarizing response, and 3/66, a hyperpolarizing response. Of C-cells, 75% gave a depolarizing response to DMPP.(ABSTRACT TRUNCATED AT 400 WORDS)


1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.


1985 ◽  
Vol 54 (6) ◽  
pp. 1375-1382 ◽  
Author(s):  
C. W. Bourque ◽  
J. C. Randle ◽  
L. P. Renaud

Intracellular recordings of rat supraoptic nucleus neurons were obtained from perfused hypothalamic explants. Individual action potentials were followed by hyperpolarizing afterpotentials (HAPs) having a mean amplitude of -7.4 +/- 0.8 mV (SD). The decay of the HAP was approximated by a single exponential function having a mean time constant of 17.5 +/- 6.1 ms. This considerably exceeded the cell time constant of the same neurons (9.5 +/- 0.8 ms), thus indicating that the ionic conductance underlying the HAP persisted briefly after each spike. The HAP had a reversal potential of -85 mV and was unaffected by intracellular Cl- ionophoresis of during exposure to elevated extracellular concentrations of Mg2+. In contrast, the peak amplitude of the HAP was proportional to the extracellular Ca2+ concentration and could be reversibly eliminated by replacing Ca2+ with Co2+, Mn2+, or EGTA in the perfusion fluid. During depolarizing current pulses, evoked action potential trains demonstrated a progressive increase in interspike intervals associated with a potentiation of successive HAPs. This spike frequency adaptation was reversibly abolished by replacing Ca2+ with Co2+, Mn2+, or EGTA. Bursts of action potentials were followed by a more prolonged afterhyperpolarization (AHP) whose magnitude was proportional to the number of impulses elicited (greater than 20 Hz) during a burst. Current injection revealed that the AHP was associated with a 20-60% decrease in input resistance and showed little voltage dependence in the range of -70 to -120 mV. The reversal potential of the AHP shifted with the extracellular concentration of K+ [( K+]o) with a mean slope of -50 mV/log[K+]o.(ABSTRACT TRUNCATED AT 250 WORDS)


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