Postnatal Development of Electrophysiological Properties of Nucleus Accumbens Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2204-2216 ◽  
Author(s):  
Marc L. Belleau ◽  
Richard A. Warren

We have studied the postnatal development of the physiological characteristics of nucleus accumbens (nAcb) neurons in slices from postnatal day 1 ( P1) to P49 rats using the whole cell patch-clamp technique. The majority of neurons (102/108) were physiologically identified as medium spiny (MS) projection neurons, and only these were subjected to detailed analysis. The remaining neurons displayed characteristics suggesting that they were not MS neurons. Around the time of birth and during the first postnatal weeks, the membrane and firing characteristics of MS neurons were quite different from those observed later. These characteristics changed rapidly during the first 3 postnatal weeks, at which point they began to resemble those found in adults. Both whole cell membrane resistance and membrane time constant decreased more than fourfold during the period studied. The resting membrane potential (RMP) also changed significantly from an average of −50 mV around birth to less than −80 mV by the end of the third postnatal week. During the first postnatal week, the current-voltage relationship of all encountered MS neurons was linear over a wide range of membrane potentials above and below RMP. Through the second postnatal week, the proportion of neurons displaying inward rectification in the hyperpolarized range increased steadily and after P15, all recorded MS neurons displayed significant inward rectification. At all ages, inward rectification was blocked by extracellular cesium and tetra-ethyl ammonium and was not changed by 4-aminopyridine; this shows that inward rectification was mediated by the same currents in young and mature MS neurons. MS neurons fired single and repetitive Na+/K+ action potentials as early as P1. Spike threshold and amplitude remained constant throughout development in contrast to spike duration, which decreased significantly over the same period. Depolarizing current pulses from rest showed that immature MS neurons fired action potentials more easily than their older counterparts. Taken together, the results from the present study suggest that young and adult nAcb MS neurons integrate excitatory synaptic inputs differently because of differences in their membrane and firing properties. These findings provide important insights into signal processing within nAcb during this critical period of development.

2001 ◽  
Vol 85 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Alexander F. Hoffman ◽  
Carl R. Lupica

The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 μM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-d-Ala2, N-CH3-Phe4, Gly-ol-enkephalin] (DAMGO, ∼35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC50 = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 μM). In contrast evIPSCs were inhibited in ∼50% of MSNs by the μ/δ opioid agonistd-Ala2-methionine2-enkephalinamide and were completely unaffected by a selective μ-opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure.


1989 ◽  
Vol 62 (6) ◽  
pp. 1280-1286 ◽  
Author(s):  
N. Uchimura ◽  
E. Cherubini ◽  
R. A. North

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.


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.


2000 ◽  
Vol 83 (5) ◽  
pp. 2649-2660 ◽  
Author(s):  
C. Peter Bengtson ◽  
Peregrine B. Osborne

The ventral pallidum is a major source of output for ventral corticobasal ganglia circuits that function in translating motivationally relevant stimuli into adaptive behavioral responses. In this study, whole cell patch-clamp recordings were made from ventral pallidal neurons in brain slices from 6- to 18-day-old rats. Intracellular filling with biocytin was used to correlate the electrophysiological and morphological properties of cholinergic and noncholinergic neurons identified by choline acetyltransferase immunohistochemistry. Most cholinergic neurons had a large whole cell conductance and exhibited marked fast (i.e., anomalous) inward rectification. These cells typically did not fire spontaneously, had a hyperpolarized resting membrane potential, and also exhibited a prominent spike afterhyperpolarization (AHP) and strong spike accommodation. Noncholinergic neurons had a smaller whole cell conductance, and the majority of these cells exhibited marked time-dependent inward rectification that was due to an h-current. This current activated slowly over several hundred milliseconds at potentials more negative than −80 mV. Noncholinergic neurons fired tonically in regular or intermittent patterns, and two-thirds of the cells fired spontaneously. Depolarizing current injection in current clamp did not cause spike accommodation but markedly increased the firing frequency and in some cells also altered the pattern of firing. Spontaneous tetrodotoxin-sensitive GABAA-mediated inhibitory postsynaptic currents (IPSCs) were frequently recorded in noncholinergic neurons. These results show that cholinergic pallidal neurons have similar properties to magnocellular cholinergic neurons in other parts of the forebrain, except that they exhibit strong spike accommodation. Noncholinergic ventral pallidal neurons have large h-currents that could have a physiological role in determining the rate or pattern of firing of these cells.


2000 ◽  
Vol 84 (3) ◽  
pp. 1681-1691 ◽  
Author(s):  
Werner Kilb ◽  
Heiko J. Luhmann

Cajal-Retzius cells are among the first neurons appearing during corticogenesis and play an important role in the establishment of cortical lamination. To characterize the hyperpolarization-activated inward current ( I h) and to investigate whether I h contributes to the relatively positive resting membrane potential (RMP) of these cells, we analyzed the properties of I h in visually identified Cajal-Retzius cells in cortical slices from neonatal rats using the whole cell patch-clamp technique. Membrane hyperpolarization to −90 mV activated a prominent inward current that was inhibited by 1 mM Cs+ and was insensitive to 1 mM Ba2+. The activation time constant for I h was strongly voltage dependent. In Na+-free solution, I h was reduced, indicating a contribution of Na+. An analysis of the tail currents revealed a reversal potential of −45.2 mV, corresponding to a permeability coefficient (pNa+/pK+) of 0.13. While an increase in the extracellular K+ concentration ([K+]e) enhances I h, it was reduced by a [K+]e decrease. This [K+]e dependence could not be explained by an effect on the electromotive force on K+ but suggested an additional extracellular binding site for K+ with an apparent dissociation constant of 7.2 mM. Complete Cl−substitution by Br−, I−, or NO3 − had no significant effect on I h, whereas a complete Cl−substitution by the organic compounds methylsulfate, isethionate, or gluconate reduced I h by ∼40%. The I h reduction observed in gluconate could be abolished by the addition of Cl−. The analysis of the [Cl−]e dependence of I h revealed a dissociation constant of 9.8 mM and a Hill-coefficient of 2.5, while the assumption of a gluconate-dependent I h reduction required an unreasonably high Hill-coefficient >20. An internal perfusion with the lidocaine derivative lidocaine N-ethyl bromide blocks I h within 1 min after establishment of the whole cell configuration. An inhibition of I h by 1 mM Cs+ was without an effect on RMP, action potential amplitude, threshold, width, or afterhyperpolarization. We conclude from these results that Cajal-Retzius cells express a prominent I hwith characteristic properties that does not contribute to the RMP.


1964 ◽  
Vol 47 (4) ◽  
pp. 719-733 ◽  
Author(s):  
W. H. Herzog ◽  
R. M. Feibel ◽  
S. H. Bryant

In the giant axon of Loligo pealii, "aconitine potent" Merck added to the bath (10-7 to 1.25 x 10-6 gm/ml) (a) had no effect on resting membrane potential, membrane resistance and rectification, membrane response to subthreshold currents, critical depolarization, or action potential, but (b) on repetitive stimulation produced oscillations of membrane potential after the spike, depolarization, and decrease of membrane resistance. The effect sums with successive action potentials; it increases with concentration of aconitine, time of exposure, and frequency of stimulation. When the oscillations are large enough and the membrane potential is 51.6 ± SD 1.5 mv a burst of self-sustained activity begins; it usually lasts 20 to 70 sec. and at its end the membrane potential is 41.5 ± SD 1.9 mv. Repolarization occurs with a time constant of 2.5 to 11.1 min. Substitution of choline for external sodium after a burst hyperpolarizes the membrane to -70 mv, and return to normal external sodium depolarizes again beyond the resting membrane potential. The effect of aconitine on the membrane is attributed to an increase of sodium and potassium or chloride conductances following the action potential.


1972 ◽  
Vol 57 (3) ◽  
pp. 609-631
Author(s):  
J. C. DELALEU ◽  
A. BLONDEAU ◽  
A. HOLLEY

1. The effects of various ions and chemicals were tested on the resting or active membrane of the heart of the wood-louse Porcellio dilatatus. 2. The curve relating the resting membrane potential to log [K+]o was found to correspond with the theoretical curve expected from the Nernst equation at higher concentrations only. Excess K+ decreased both amplitude and rate of rise of the response while the rate of decline was increased. In K+-deficient solutions the duration of the plateau phase was at first increased, then depressed. The addition of K+ to a bathing medium deprived for several minutes of this ion caused a large increase in the membrane potential and in the response height. The way in which the membrane was seen to react was tentatively attributed to an electrogenic active pumping mechanism. 3. In Na+-deficient solutions, the rate of rise and the height of the response were reduced while the resting membrane potential was decreased. 4. Ca2+-deficient solutions depolarized the membrane and decreased both amplitude and duration of the response. Cessation of activity occurred in Ca2+-free solution. In excess calcium the membrane was hyperpolarized. The rhythm and the rate of rising were decreased and the plateau phase depressed. 5. TTX blocked the heart activity, probably by acting upon the heart ganglion. Mn2+ depressed especially the humped plateau (when present) of the spontaneous responses. 6. TEA, caffeine and procaine transformed spontaneous activity of weak amplitude into large and complex overshooting responses. In TEA solutions, several stable levels of polarization were observed. Contrary to what occurred in the normal solution, depolarizing current pulses could trigger large all-or-none action potentials when TEA was present. 7. The TEA-induced regenerative response was analysed with the help of an intracellular stimulating current when [Na+]o and [Ca2+]o were varied. Additional data were obtained by applying TTX, Mn2+ or GABA. From the results, both Ca2+ and Na+ were thought to be involved in the ionic currents underlying spike type activity. 8. The spike-generating effect of TEA has been attributed to its property of increasing the membrane resistance and of allowing the ionic conductances which generate the weakly active component of the normal response, the plateau, but not the initial upstroke, to be amplified regeneratively. 9. The large spikes elicited by TEA were found relatively less effective than weak sustained depolarization in inducing strong contractions. 10. The functional significance of the data was tentatively interpreted by comparison with the properties of the heart of Limulus, Crustacea and vertebrates.


2004 ◽  
Vol 92 (3) ◽  
pp. 1597-1607 ◽  
Author(s):  
Xiu-Ti Hu ◽  
Somnath Basu ◽  
Francis J. White

The nucleus accumbens (NAc) is an important forebrain area involved in sensitization, withdrawal effects, and self-administration of cocaine. However, little is known about cocaine-induced alterations in the neuronal excitability and whole cell neuroplasticity in this region that may affect behaviors. Our recent investigations have demonstrated that repeated cocaine administration decreases voltage-sensitive sodium and calcium currents (VSSCs and VSCCs, respectively) in freshly dissociated NAc neurons of rats. In this study, current-clamp recordings were performed in slice preparations to determine the effects of chronic cocaine on evoked Ca2+ potentials and voltage-sensitive K+ currents in NAc neurons. Repeated cocaine administration with 3–4 days of withdrawal caused significant alterations in Ca2+ potentials, including suppression of Ca2+-mediated spikes, increase in the intracellular injected current intensity required for generation of Ca2+ potentials (rheobase), reduced duration of Ca2+ plateau potentials, and abolishment of secondary Ca2+ potentials associated with the primary Ca2+ plateau potential. Application of nickel (Ni2+), which blocks low-voltage activated T-type Ca2+ channels, had no impact on evoked Ca2+ plateau potentials in NAc neurons, indicating that these Ca2+ potentials are high-voltage activated (HVA). In addition, repeated cocaine pretreatment also hyperpolarized the resting membrane potential, increased the amplitude of afterhyperpolarization in Ca2+ spikes, and enhanced the outward rectification observed during membrane depolarization. These findings indicate that repeated cocaine administration not only suppressed HVA-Ca2+ potentials but also significantly enhanced the activity of various K+ channels in NAc neurons. They also demonstrate an integrative role of whole cell neuroplasticity during cocaine withdrawal, by which the subthreshold membrane excitability of NAc neurons is significantly decreased.


2006 ◽  
Vol 290 (4) ◽  
pp. C1009-C1017 ◽  
Author(s):  
Luiz Artur Poletto Chaves ◽  
Endrigo Piva Pontelli ◽  
Wamberto Antonio Varanda

ATP-activated currents were studied in Leydig cells of mice with the patch-clamp technique. Whole cell currents were rapidly activating and slowly desensitizing (55% decrement from the peak value on exposure to 100 μM ATP for 60 s), requiring 3 min of washout to recover 100% of the response. The concentration-response relationships for ATP, adenosine 5′- O-(3-thiotriphosphate) (ATPγS), and 2-methylthio-ATP (2-MeS-ATP) were described by the Hill equation with a concentration evoking 50% of maximal ATP response ( Kd) of 44, 110, and 637 μM, respectively, and a Hill coefficient of 2. The order of efficacy of agonists was ATP ≥ ATPγS > 2-MeS-ATP > 2′,3′- O-(4-benzoylbenzoyl)-ATP (BzATP). αβ-Methylene-ATP (αβ-MeATP), GTP, UTP, cAMP, and adenosine were ineffective. Suramin and pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) blocked the responses in a concentration-dependent manner. The ATP-activated currents were dependent on extracellular pH, being maximal at pH 6.5 and decreasing with both acidification and alkalinization (apparent dissociation constant (p Ka) of 5.9 and 7.4, respectively). The whole cell current-voltage relationship showed inward rectification and reversed near 0 mV. Experiments performed in bi-ionic conditions for measurement of reversal potentials showed that this channel is highly permeable to calcium [permeability ( P)Ca/ PNa = 5.32], but not to chloride ( PCl/ PNa = 0.03) or N-methyl-d-glucamine (NMDG) ( PNMDG/ PNa = 0.09). Unitary currents recorded in outside-out patches had a chord conductance of 27 pS (between −90 and −50 mV) and were inward rectifying. The average current passing through the excised patch decreased with time [time constant (τ) = 13 s], resembling desensitization of the macroscopic current. These findings indicate that the ATP receptor present in Leydig cells shows properties most similar to those of cloned homomeric P2X2.


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