scholarly journals A1 adenosine receptor-mediated GIRK channels contribute to the resting conductance of CA1 neurons in the dorsal hippocampus

2015 ◽  
Vol 113 (7) ◽  
pp. 2511-2523 ◽  
Author(s):  
Chung Sub Kim ◽  
Daniel Johnston

The dorsal and ventral hippocampi are functionally and anatomically distinct. Recently, we reported that dorsal Cornu Ammonis area 1 (CA1) neurons have a more hyperpolarized resting membrane potential and a lower input resistance and fire fewer action potentials for a given current injection than ventral CA1 neurons. Differences in the hyperpolarization-activated cyclic nucleotide-gated cation conductance between dorsal and ventral neurons have been reported, but these differences cannot fully account for the different resting properties of these neurons. Here, we show that coupling of A1 adenosine receptors (A1ARs) to G-protein-coupled inwardly rectifying potassium (GIRK) conductance contributes to the intrinsic membrane properties of dorsal CA1 neurons but not ventral CA1 neurons. The block of GIRKs with either barium or the more specific blocker Tertiapin-Q revealed that there is more resting GIRK conductance in dorsal CA1 neurons compared with ventral CA1 neurons. We found that the higher resting GIRK conductance in dorsal CA1 neurons was mediated by tonic A1AR activation. These results demonstrate that the different resting membrane properties between dorsal and ventral CA1 neurons are due, in part, to higher A1AR-mediated GIRK activity in dorsal CA1 neurons.

1993 ◽  
Vol 70 (5) ◽  
pp. 1975-1987 ◽  
Author(s):  
S. M. Johnson ◽  
R. B. Felder

1. Recent studies have demonstrated that the arterial baroreflex is imparied with aging and have implicated central components of the baroreflex arc in this autonomic dysfunction. Neurons in the medial portion of the nucleus tractus solitarius (mNTS) receive a major input from the arterial baroreceptors. The present study was undertaken to characterize the intrinsic membrane properties of mNTS neurons in young rats and to test the hypothesis that these properties are altered with aging. An in vitro brain stem slice preparation was used to record intracellularly from mNTS neurons; passive membrane properties, action potential characteristics, and repetitive firing properties were examined and compared. 2. Neurons in the mNTS of young (3-5 mo old) Fischer-344 rats (F-344; n = 35) had a resting membrane potential of -57 +/- 6.9 mV (mean +/- SD), a membrane time constant of 18 +/- 9.0 ms, and an input resistance of 110 +/- 60 m omega. Action potential amplitude was 81 +/- 7.5 mV with a duration at half-height of 0.83 +/- 0.15 ms. The spontaneous firing rate in 24 cells was 4.3 +/- 2.9 Hz. The amplitude and duration of the action potential afterhyperpolarization (AHP) were 6.6 +/- 3.0 mV and 64 +/- 34 ms, respectively. All neurons expressed spike frequency adaptation, action potential AHP, and posttetanic hyperpolarization. Delayed excitation and postinhibitory rebound were present in 34 and 14% of neurons tested, respectively. Neurons from adult (10-12 mo old) F-344 rats (n = 34) were similar to the young F-344 rats with respect to all of these variables. 3. Neurons from aged (21-24 mo old) F-344 (n = 32) were similar to those from young and adult rats, but there were two potentially important differences: the mean input resistance of the aged neurons was higher (170 +/- 150 M omega), with a larger proportion (46% of aged neurons vs. 20% of young neurons and 21% of adult neurons) having input resistances > 150 M omega; and there was a tendency for a smaller percentage of aged neurons (16% of aged neurons vs. 34% of young neurons and 29% of adult neurons) to express delayed excitation. 4. The potential significance of a high input resistance was tested by comparing the steady-state current-voltage (I-V) relationships and the frequency-current (f-I) relationships among low-resistance (1-100 M omega), medium-resistance (101-200 M omega).(ABSTRACT TRUNCATED AT 400 WORDS)


2003 ◽  
Vol 90 (1) ◽  
pp. 405-414 ◽  
Author(s):  
Regula E. Egli ◽  
Danny G. Winder

The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.


2002 ◽  
Vol 87 (5) ◽  
pp. 2398-2407 ◽  
Author(s):  
Carmen Cabanes ◽  
Mikel López de Armentia ◽  
Félix Viana ◽  
Carlos Belmonte

Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0–P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Aδ and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance ( R in), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Aδ, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Aδ neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca2+ or substitution with Co2+ during the process of maturation.


1998 ◽  
Vol 79 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Gytis Svirskis ◽  
Jørn Hounsgaard

Svirskis, Gytis and Jørn Hounsgaard. Transmitter regulation of plateau properties in turtle motoneurons. J. Neurophysiol. 79: 45–50, 1998. In motoneurons, generation of plateau potentials is promoted by modulators that block potassium channels. In voltage-clamp experiments with triangular voltage ramp commands, we show that cis-(±)-1-aminocyclopentane-1,3-dicarboxylic acid ( cis-ACPD) and muscarine promote the generation of plateau potentials by increasing the dihydropyridine sensitive inward current, by increasing the input resistance, and by depolarizing the resting membrane potential. Type I metabotropic glutamate receptors (mGluR I) mediate the effects of cis-ACPD. Baclofen suppresses generation of plateau potentials by decreasing the dihydropyridine sensitive inward current, by decreasing the input resistance, and by hyperpolarizing the resting membrane potential. These results suggest that membrane properties of motoneurons are continuously modulated by synaptic activity in ways that may have profound effects on synaptic integration and pattern generation.


2004 ◽  
Vol 21 (2) ◽  
pp. 135-144 ◽  
Author(s):  
SALLY W. ABOELELA ◽  
DAVID W. ROBINSON

The ganglion cell layer (GCL) of the mammalian retina contains a large number of neurons called displaced amacrine cells (DACs) that do not project to the optic nerve. However, with the exception of the rabbit starburst amacrine cell little is known regarding the function of this large population due to the difficulty experienced in making physiological recordings from these neurons. We have overcome these difficulties and have used whole-cell patch-clamp techniques to examine the intrinsic membrane properties of DACs in the ferret retina. Our results indicate a large degree of diversity in their intrinsic membrane properties. In response to maintained depolarizing current injection, DACs responded with graded depolarization or by eliciting either transient or sustained bursts of spiking activity. At the resting membrane potential, 10% of the DACs generated spontaneous spikes in either an apparently random manner or at the peak of intrinsic waves of depolarization. The resting membrane activity of the remaining DACs recorded could be classified into three groups that were quiescent (28%), had robust uncorrelated synaptic activity (30%), or underwent slow waves of depolarization (42%). Diversity was also revealed in the membrane currents recorded in voltage-clamp where some DACs were quiescent (19%), or exhibited robust nonrhythmic synaptic events (42%). The remaining DACs exhibited waves of oscillatory activity (39%), characterized by either rhythmic bursts of synaptic events (17%) or slow inward currents (22%). Bath application of 50 μM biccuculine or 150 μM picrotoxin had no effect on the waves of activity, however, the gap junction blocker, carbenoxolone (100 μm), blocked both oscillatory patterns. By including Lucifer yellow and biocytin in the recording pipette, it was possible to determine the morphology of recorded neurons and group them based on dendritic extent as small-, medium-, or large-field DACs. There were few relationships between these morphologically defined groups and their intrinsic membrane properties. The present study provides the first in-depth examination of the intrinsic membrane properties of DACs in the ferret retina and provides new insights into the potential roles these neurons play in the processing of visual information in the mammalian retina.


1993 ◽  
Vol 70 (3) ◽  
pp. 1244-1248 ◽  
Author(s):  
D. Mattia ◽  
G. G. Hwa ◽  
M. Avoli

1. Conventional intracellular recordings were performed in rat hippocampal slices to investigate the electrophysiological properties of subicular neurons. These cells had a resting membrane potential (RMP) of -66 +/- 7.2 mV (mean +/- SD; n = 50), input resistance of 23.6 +/- 8.2 M omega (n = 51), time constant of 7.1 +/- 1.9 ms (n = 51), action potential amplitude of 85.8 +/- 13.8 mV (n = 50), and duration of 2.9 +/- 1.2 ms (n = 48). Analysis of the current-voltage relationship revealed membrane inward rectification in both depolarizing and hyperpolarizing direction. The latter type was readily abolished by Cs+ (3 mM; n = 6 cells). 2. Injection of depolarizing current pulses of threshold intensity induced in all subicular neurons (n = 51) recorded at RMP a burst of two to three fast action potentials (frequency = 212.7 +/- 90 Hz, n = 13 cells). This burst rode on a slow depolarizing envelope and was followed by an afterhyperpolarization and later by regular spiking mode once the pulse was prolonged. Similar bursts were also generated upon termination of a hyperpolarizing current pulse. 3. The slow depolarization underlying the burst resembled a low-threshold response, which in thalamic cells is caused by a Ca2+ conductance and is contributed by the Cs(+)-sensitive inward rectifier. However, bursts in subicular cells persisted in medium containing the Ca(2+)-channel blockers Co2+ (2 mM) and Cd2+ (1 mM) (n = 5 cells) but disappeared during application of TTX (1 microM; n = 3 cells). Hence they were mediated by Na+. Blockade of the hyperpolarizing inward rectification by Cs+ did not prevent the rebound response (n = 3 cells). 4. Our findings demonstrate that intrinsic bursts, presumably related to a "low-threshold" Na+ conductance are present in rat subicular neurons. Similar intrinsic characteristics have been suggested to underlie the rhythmic activity described in other neuronal networks, although in most cases the low-threshold electrogenesis was caused by Ca2+. We propose that the bursting mechanism might play a role in modulating incoming signals from the classical hippocampal circuit within the limbic system.


1996 ◽  
Vol 75 (1) ◽  
pp. 248-267 ◽  
Author(s):  
G. F. Tseng ◽  
D. A. Prince

1. The electrophysiological properties of rat corticospinal neurons (CSNs) were studied 3, 9, and 12 mo after axotomy in the cervical spinal cord, with the use of a combination of the in vitro neocortical slice technique, intracellular recordings, and a double-labeling method that allowed identification of CSNs studied in vitro. 2. CSNs retained the rhodamine-labeled microspheres employed as a retrograde marker and were functionally active in the longest survival group (1 yr). 3. The somatic area of axotomized CSNs became progressively smaller, a reduction that amounted to 37% for all cells at 1 yr. There were no obvious differences between normal and axotomized cells in terms of apical dendritic widths, numbers of apical dendritic branches, or basal dendritic arbors. Intracortical axonal arborizations of axotomized neurons were in general similar to those of normal CSNs in that most axons ended in layers V and VI with only occasional collaterals reaching supragranular layers. 4. Axotomized CSNs were grouped according to their spike firing patterns during depolarizing current pulses so that their electrophysiological behavior could be compared with that of regular spiking and adapting groups of normal CSNs. No significant differences were found in resting membrane potential, or spike parameters between axotomized neurons in any survival group and normal controls. Neurons surviving 1 yr after axotomy had a higher input resistance (RN) than normal CSNs. There was a reduction in the percentage of CSNs that generated prominent spike depolarizing afterpotentials in the axotomized group. 5. The steady-state relationship between spike frequency and applied current (f-I slope) became steeper over time and was significantly greater 9 mo after axotomy in regular spiking (RS) and adapting neurons than in normal CSNs in the same groups. The increase in steady-state f-I slope was in part related to increases in the RN of axotomized neurons. 6. There was a significant decrease in the generation of slow afterhyperpolarizations following trains of spikes in axotomized versus normal RS neurons, first detected at 3 mo and also present in 9 mo and 1 yr survival groups. 7. Biphasic inhibitory postsynaptic potentials (IPSPs) were evoked in only 1 of 11 axotomized neurons in the 3-mo group, 2 of 12 cells examined at 9 mo, and 3 of 15 neurons 1 yr after axotomy. The proportions of neurons generating IPSPs were significantly smaller than in comparable groups of control CSNs. As a consequence, longer duration evoked excitatory postsynaptic potentials were generated by axotomized CSNs. 8. Results show that axotomized CSNs undergo alterations in intrinsic membrane properties and inhibitory synaptic electrogenesis that would tend to make them more responsive to excitatory inputs.


2008 ◽  
Vol 99 (2) ◽  
pp. 958-968 ◽  
Author(s):  
Lutz Liebmann ◽  
Henk Karst ◽  
Kyriaki Sidiropoulou ◽  
Neeltje van Gemert ◽  
Onno C. Meijer ◽  
...  

The stress hormone corticosterone increases the amplitude of the slow afterhyperpolarization (sAHP) in CA1 pyramidal neurons, without affecting resting membrane potential, input resistance, or action potential characteristics. We here examined how corticosterone affects these properties in the basolateral amygdala (BLA). In the amygdala, corticosterone does not change the AHP amplitude, nor any of the passive and active membrane properties studied. The lack of effect on the AHP is surprising since in both areas corticosterone increases high-voltage–activated sustained calcium currents, which supposedly regulate the sAHP. We wondered whether corticosterone targets different calcium channel subunits in the two areas because currents through only one of the subunits (Cav1.3) are thought to alter the AHP amplitude. In situ hybridization studies revealed that CA1 cells express Cav1.2 and Cav1.3 subunits; corticosterone does not transcriptionally regulate Cav1.2 but increases Cav1.3 expression compared with vehicle treatment. In the BLA, Cav1.3 expression was not detectable, both after control and corticosterone treatment. Cav1.2 is moderately expressed. In a modeling study, we examined putative consequences of changes in specific calcium channel subunit expression and calcium extrusion by corticosterone for the AHP in CA1 and amygdala neurons. A differential distribution and transcriptional regulation of Cav1.2 and Cav1.3 in the CA1 area versus BLA partly explain the observed differences in AHP amplitude. The functional implication of these findings could be that stress-induced arousal of activity in the BLA is more prolonged than that in the CA1 hippocampal area, so that information with an emotional component is more effectively encoded.


2010 ◽  
Vol 103 (6) ◽  
pp. 3001-3016 ◽  
Author(s):  
Michael J. Pesavento ◽  
Cynthia D. Rittenhouse ◽  
David J. Pinto

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.


1990 ◽  
Vol 69 (4) ◽  
pp. 1509-1517 ◽  
Author(s):  
G. G. Haddad ◽  
D. F. Donnelly ◽  
P. A. Getting

A brain stem slice preparation from adult and neonatal (less than or equal to 12 days old) rats and intracellular recordings were used to examine the cellular properties of neurons within the hypoglossal (HYP) nucleus. Resting membrane potential (Vm) for adult hypoglossal neurons was -80 +/- 2 (SE) mV. Rheobase was 2.1 +/- 0.4 nA, and input resistance (RN) was 20.8 +/- 1.5 M omega and decreased during the hyperpolarizing period ("sag"). Compared with adult HYP cells, newborn HYP neurons had significantly lower resting potentials (Vm = -73 +/- 2 mV), lower rheobase (0.7 +/- 0.2 nA), and higher RN (27.6 +/- 3.9 M omega). Single action potentials, elicited by short depolarizing-current pulses, were followed by a slow afterhyperpolarization in adult [6.4 +/- 0.3 mV, time constant (tc) 31.0 +/- 1.2 ms] and newborn cells (7.4 +/- 0.2 mV, tc 37.2 +/- 8.2 ms). Prolonged outward current (2 s) produced little spike frequency adaptation in either adult or newborn neurons. Onset of spike activity was not delayed by hyperpolarizing pulses preceding depolarizations. In addition, pharmacological experiments showed that HYP neurons have a tetrodotoxin-sensitive Na+ current and a delayed and an inward rectifier current but no major Ca2+ current. We conclude the following. 1) Electrophysiological membrane properties mature postnatally in HYP neurons; some of these developmental changes can be ascribed to an increase in soma size and dendritic outgrowth but others cannot. 2) Adult HYP neurons, compared with other brain stem neurons (i.e., vagal cells or cells in the nucleus tractus solitarius), are not endowed with major Ca2+ currents or K+ currents such as the A current and the Ca2(+)-activated K+ current.


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