Bath Application Of Norepinephrine Research Articles

A role for nerve growth factor in sympathetic sprouting in rat dorsal root ganglia

The role of nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) in sympathetic sprouting within the dorsal root ganglion was investigated. In nerve-intact rats, intrathecal NGF (1 mg/ml, 14 days) but not GDNF (1 mg/ml, 14 days) induced extensive sprouting of tyrosine hydroxylase immunoreactive (TH-IR) fibres and formation of pericellular TH-IR baskets within lumbar DRGs. TH-IR baskets were distributed equally to trkA-expressing and trkA-negative neuronal profiles. Sciatic nerve transection (14–21 days) induced TH-IR baskets within lumbar DRG's around neuronal profiles with both intact and lesioned axons. The percentage of neuronal profiles surrounded by TH-IR baskets following sciatic transection was unaffected following peripheral application of the NGF sequestering antibody, trkA-IgG (1 mg/ml, 14 days). Intracellular responses were recorded from sensory neurons in an in vitro DRG/peripheral nerve preparation following bath application of noradrenaline. In preparations from animals treated 14 days previously with intrathecal NGF, 69% of neurons responded with depolarizing responses whilst 18% of neurons responded to bath applied noradrenaline in tissue prepared from naive animals. Our data indicate that sympathetic neurons sprout into the DRG in response to sciatic nerve injury and intrathecal NGF but not GDNF. Distribution of sympathetic sprouts within the DRG is independent of whether target neurons are injured or express trkA. Sequestration of NGF at the peripheral injury site does not influence basket formation within the DRG. It is likely that functional noradrenergic connections exist between sympathetic sprouts and sensory neuron cell bodies following exogenous NGF.

Norepinephrine inhibits neurons of the intermediate subnucleus of the lateral septum via α 2-adrenoceptors

The physiological and pharmacological actions of norepinephrine (NE) on neurons of the intermediate subnucleus of the lateral septum (LSI) were examined using intracellular recordings in rat brain-slices. Bath-applied NE inhibited 72.5%, excited 5.5% and had no effect on 22% of LSI neurons tested; this study focused on the inhibitory effects of NE. In current clamp recordings, 100 μM NE produced a hyperpolarization of 10.82±0.72 mV ( n=84) with a decrease in input resistance. In voltage-clamp, NE produced a direct, post-synaptic outward current of 206.8±22 pA ( n=37) with a 64.3±4.9% increase in input conductance (IC 50—17.7±4 μM). The NE-induced inhibition was mimicked by the α 2-agonist, UK14,304, but not by the α 1- or β-adrenoceptor agonists. The α 2-agonist, clonidine, had a weak effect in LSI neurons. Interestingly, the magnitude of the UK14,304-induced response varied between cells (ranging from 29.5 to 320% of the maximal NE inhibition), possibly suggesting the involvement of α 2A-(high affinity for UK14,304) and non-α 2A (low affinity for UK14,304) adrenoceptor subtypes. While the α 2-antagonists, yohimbine, rauwolscine and idazoxan blocked NE-induced inhibition in all neurons tested, the prototypical α 1-antagonist, prazosin produced a variable degree of block (9–58%), further indicating the possible involvement of α 2A (prazosin-insensitive) and non-α 2A (prazosin-sensitive) receptors. However a lack of more selective pharmacological tools precludes definitive classification of the α 2-receptor-mediated responses into different subtypes. The α 2-receptor-mediated current in LSI neurons displayed Ba 2+-sensitive inward rectification, reversed polarity near E K and was sensitive to external K +. In conclusion, NE inhibits LSI neurons via α 2-adrenoceptor subtypes.

Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices.

Whole cell voltage-clamp recordings were performed on auditory olivocochlear neurons in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of norepinephrine (NE; 1-10 microM) reversibly induced an inward current in 26 of 38 labeled neurons that were voltage clamped at -75 mV. This was responsible for the membrane depolarization to NE observed in current-clamp mode. The NE-induced inward current appeared to be more prominent at -55 mV than at -75 mV and reversed at around -100 mV. It was attenuated but not prevented by 20 mM tetraethylammonium, and it persisted when the perfusate contained 2 mM Cs+ or 100 microM Cd2+. However, the NE-induced inward current was attenuated to varying degrees in a zero-Ca2+ solution. Current-voltage plots revealed that NE caused a decrease in membrane K+ conductance. A suppression of voltage-gated Ca2+ currents by NE was also observed. The excitatory action of NE was blocked by the alpha-adrenoreceptor antagonist phentolamine. The alpha1-adrenoreceptor agonist phenylephrine had an effect similar to that of NE. In 6 of 38 labeled neurons, an inhibitory action of NE (1-10 microM) was observed that appeared to be due to an activation of an inwardly rectified K+ current, which caused hyperpolarization of resting membrane potentials in current-clamp mode. This inhibitory response was independent of external Ca2+ and was abolished by 2-5 mM Cs+ or 0.5 mM Ba2+ applied in the perfusate. The receptors involved in the inhibitory actions of NE are not clear. The effect was partially and reversibly blocked by propranolol (10 microM), a beta-adrenoreceptor antagonist. However, isoprenaline (10 microM), a beta-adrenoreceptor agonist, failed to induce any effect. On the other hand, the inhibitory effect was irreversibly blocked by pretreatment with phentolamine (5-10 microM). Phenylephrine (5-10 microM) had no effect.

Alpha 1-adrenoceptor activation of a non-selective cation current in rabbit portal vein by 1,2-diacyl-sn-glycerol.

1. The transduction mechanisms involved in the activation and modulation of the noradrenaline-activated cation current (Icat) were investigated with whole-cell patch clamp techniques in rabbit portal vein smooth muscle cells. 2. Intracellular application of guanosine 5-O-(3-thiotriphosphate) (GTP gamma S, 500 microM) evoked a 'noisy' inward current at -50 mV with a similar current-voltage relationship and reversal potential to the current evoked by bath application of noradrenaline (100 microM). Guanosine 5-O-(2-thiodiphosphate) (GDP beta S, 1 mM) markedly inhibited noradrenaline-activated Icat. 3. The phospholipase C (PLC) inhibitor U73122 inhibited the amplitude of the noradrenaline-activated Icat in a concentration- and time-dependent manner and the IC50 was about 180 nM. U73122 had similar effects on the cation current evoked by GTP gamma S. 4. Intracellular application of myo-inositol 1,4,5-trisphosphate (IP3, 100 microM) from the patch pipette did not activate any membrane current in cells where intracellular calcium concentration ([Ca2+]i) was buffered to 14 nM, but subsequent addition of noradrenaline evoked Icat. 5. Bath application of the 1,2-diacyl-sn-glycerol (DAG) analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG, 10 microM) activated Icat, whereas the phorbol ester phorbol 12,13-dibutyrate (PDBu, 0.1-5 microM) failed to activate Icat, in every cell examined. Icat activated by OAG after bath application of PDBu was not significantly different from OAG-activated Icat in the absence of PDBu. The DAG lipase inhibitor RHC80267 (10 microM) activated Icat in some cells, whereas the DAG kinase inhibitor R59949 (10 microM) never activated Icat. 6. Bath application of the protein kinase C inhibitor chelerythrine (1-10 microM) had no effect on either OAG-or noradrenaline-activated Icat. 7. It is concluded that noradrenaline activates Icat via a G-protein coupled to PLC and that the resulting DAG product plays a central role in the activation of cation channels via a protein kinase C-independent mechanism.

Melanophores in Damselfish Neurofibromatosis: Alterations in Morphology and Melanosome Aggregation Responses

Abstract Damselfish neurofibromatosis (DNF) is a neoplastic disease affecting bicolor damselfish Pornacentrus partitus on south Florida reefs. This disease exhibits many traits in common with neurofibromatosis type-1 in humans, including multiple plexiform neurofibromas and areas of hyperpigmentation. An important issue in understanding the pathogenesis of DNF is the relation between chromatophores and other cell types that give rise to tumors in this disease. Melanophores cultured from tumors of fish with DNF were compared in vitro with cells from normal skin of healthy fish to determine if these cells were morphologically or physiologically altered in this disease. Melanophores from tumors were significantly larger in cross-sectional perimeter and area than normal counterparts. Pigment translocation responses were measured by bath application of norepinephrine. At drug concentrations of 5 × 10-9 to 5 × 10-5 M, significantly fewer tumorderived cells than normal cells exhibited complete melanosome aggrega...

Adrenergic calcium signaling in astrocyte networks within the hippocampal slice

Norepinephrine (NE) and glutamate (Glu) initiate intracellular calcium ([Ca2+]i) transients, oscillations, and intracellular [Ca2+]i waves in cultured astrocytes. To further elucidate the significance of NE- and Glu-evoked astrocytic [Ca2+]i signaling to neuron-astrocyte communication in the mature CNS, [Ca2+]i of astrocyte networks within hippocampal slices (P21-42) was measured during bath application of NE and Glu receptor agonists. Astrocytes in stratum radiatum were identified by highly negative membrane potentials (75 +/- 3 mV), absence of action potentials, and dye coupling following intracellular injection of the [Ca2+]-sensitive dye calcium orange. NE (2-100 microM) evoked [Ca2+]i increases (7 of 8 slices, 24 of 24 cells in responding slices) characterized by an initial rise, 20-50 sec to peak, followed by a slower return to baseline (over approximately 8 min). The alpha 1-agonist phenylephrine (PE) (10-100 microM) evoked complex [Ca2+]i signals (22 of 26 slices, 90 of 90 cells in responding slices) composed of both a prolonged component (5.1 +/- 1.8 min), synchronized in neighboring cells, and multiple, mainly asynchronous [Ca2+]i spikes (25.0 +/- 11.6 sec). PE responses were completely blocked by the alpha 1-antagonist prazosin (200 nM, n = 4 slices), but not by the alpha 2-antagonist yohimbine (n = 3 slices). The alpha 2-agonist clonidine (10-100 microM) did not increase [Ca2+]i (n = 4 slices). alpha 1-mediated [Ca2+]i transients were observed after removal of extracellular [Ca2+]o (n = 8 of 9 slices), indicating PE-induced Ca2+ release from intracellular stores. Adrenergic responses were mediated by alpha 1-receptors localized to astrocytes because PE and NE increased [Ca2+]i of acutely isolated hippocampal astrocytes. Glu (0.75-2.0 mM) did not increase astrocytic [Ca2+]i in slices (0 of 7), even in the presence of the Glu uptake inhibitor L-trans-pyrrollidine-2,4-dicarboxylic acid (PDC) (0 of 5 slices), or in acutely isolated astrocytes (0 of 7 cells). The metabotropic agonist t-ACPD (30 or 50 microM) did not increase astrocytic [Ca2+]i in hippocampal slices (0 of 5), while kainate (200 microM or 1 mM) induced brief (1-2 min) [Ca2+]i increases only rarely (2 of 8 applications in 6 slices). These results support a primary role of NE release and alpha 1-adrenoceptor stimulation in neuron-astrocyte communication in the mature CNS.

Respiratory Rhythm In The Isolated Central Nervous System Of Newborn Opossum

1. Respiratory activity was recorded from spinal ventral roots in the isolated intact central nervous system (CNS) of newborn opossum, Monodelphis domestica. These signals occurred in synchrony with movements of the ribs and the electromyogram (EMG) recorded from the intercostal muscles during inspiration. Rhythmical activity could be recorded for more than 6 h in acute preparations. 2. The rhythm-generating region was shown to be located in the lower brain stem by perfusing different CNS regions with medium containing 20 mmoll-1 Mg2+, which blocks synaptic transmission reversibly in the opossum CNS. The conclusion that respiration was generated by neurones in the lower brain stem was further confirmed by selective ablation of part of the CNS. 3. Recordings were made from 128 neurones in the respiratory region of the lower brain stem with activity related to the respiratory rhythm. They consisted of two inspiratory groups and two expiratory groups. In the groups of inspiratory units, recordings were made from 69 early inspiratory and 38 inspiratory units. In the groups of expiratory units, recordings were made from 17 post-inspiratory and 4 expiratory units. The sites of 22 respiratory neurones were marked in 4-day-old animals by injecting Pontamine Sky Blue. These neurones were distributed from 175 microns anterior to 525 microns posterior to the obex, from 225 to 450 microns lateral to the midline and from 175 to 425 microns deep to the ventral surface of the brain stem. 4. The respiratory rhythm recorded in the isolated CNS was influenced by pH and neurotransmitters. The respiratory rate decreased by about 26% at high pH (7.7) and increased by about 33% at low pH (7.1). Bath application of noradrenaline (30-100 mumol l-1) decreased the respiratory rate and increased the amplitude of the rhythmic bursts significantly. All these effects were reversible. 5. The results presented here indicate that the isolated intact CNS of newborn opossum offers advantages for exploring mechanisms responsible for generating the respiratory rhythm.

Norepinephrine modulates excitatory amino acid-induced responses in developing human and adult rat cerebral cortex

These experiments were designed to assess the ability of norepinephrine and its β-receptor agonist, isoproterenol, to modulate responses induced by activation of excitatory amino acid receptors in brain slices obtained from developing human cortex or adult rat cortex. Human cortical slices were obtained from children undergoing surgery for intractable epilepsy (9 months to 10 yr of age). For comparison, slices were also obtained from rats (2–3 months of age). Iontophoretic application of glutamate, N-methyl-d-aspartate or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) produced excitatory responses consisting of membrane depolarizations accompanied by action potentials. Iontophoretic or bath application of norepinephrine or isoproterenol enhanced responses evoked by glutamate or N-methyl-d-aspartate. Depolarizations occurred with shorter latencies and their amplitudes increased. Action potential frequency was also increased and responses were of longer duration. In contrast, norepinephrine or isoproterenol had no effect on responses induced by AMPA. The enhancement of responses induced by N-methyl-d-aspartate or glutamate was antagonized by the β-adrenergic receptor antagonist propranolol. Similar findings were obtained from neurons in humans or rats.These results suggest that norepinephrine, possibly via β-receptors, potentiates responses mediated by glutamate and N-methyl-d-aspartate receptors without affecting those mediated by AMPA receptors. These effects were observed at all ages studied, indicating that the ability of norepinephrine to modulate excitatory neuronal transmission is well developed in human cortex by 9 months of age.

Noradrenaline mediates paradoxical effects on rat neocortical neurons after GABA withdrawal

1. The aim of the present study was to determine the role of noradrenergic neurotransmission in neuronal activities intracellularly recorded in neocortical slices obtained from rats presenting the gamma-aminobutyric acid (GABA) withdrawal syndrome (GWS), a focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion into the somatomotor cortex. Neurons recorded in the epileptic focus area (n = 52) were bursting or nonbursting cells. Intrinsic bursting (IB, n = 20) cells presented bursts of action potentials (APs) to an intracellular depolarizing current injection and paroxysmal depolarization shifts (PDSs) to white matter stimulation. Synaptic bursting (SB, n = 22) cells presented only PDSs. Nonbursting (NB, n = 10) cells presented no burst after either synaptic stimulation or depolarizing current injection. Results were compared with those obtained from NB neurons (n = 4) recorded in slices from saline-infused rats. 2. In all of the recorded neurons, bath application of norepinephrine (NE, 10 and 100 microM) provoked a depolarization (1-5 mV) associated with a decrease in input K+ conductance having a mean reversal potential at -90 to -102 mV, not significantly different for bursting and nonbursting cells. This reversal potential differed from that of Cl(-)-mediated inhibitory postsynaptic potentials (-70 mV) elicited in NB cells by electrical stimulation of the white matter. 3. In IB cells, the NE-induced depolarization replaced the intrinsic bursts by a sustained repetitive discharge of single APs and caused intrinsic bursts to appear during previously subthreshold depolarizing current pulses. These NE-increased activities were abolished by dihydropyridine nitrendipine (1 microM) and by Cd2+ (0.5 mM) or Co2+ (2 mM), thus confirming that Ca2+ currents contribute to burst generation in IB cells. 4. In both NB and SB cells recorded in slices from GWS rats, NE provoked the appearance of intrinsic bursts of APs during steps of depolarizing current injections. In addition, in NB cells, NE caused synaptic bursts to appear after white matter stimulation. These NE-induced bursts were dihydropyridine (nitrendipine, 1 microM)- and Cd2+ (0.5 mM)- or Co2+ (2 mM)-sensitive and were related to an increased AP-afterdepolarization. The fast AP-afterhyperpolarization was not affected by NE. In NB cells recorded in slices from saline-infused rats (n = 4) NE did not provoke the appearance of bursts even when stimulation intensity was increased up to three times.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane responses to norepinephrine in cultured brown fat cells.

We used the "perforated-patch" technique (Horn, R., and A. Marty, 1988. Journal of General Physiology. 92:145-159) to examine the effects of adrenergic agonists on the membrane potentials and membrane currents in isolated cultured brown fat cells from neonatal rats. In contrast to our previous results using traditional whole-cell patch clamp, 1-23-d cultured brown fat cells clamped with the perforated patch consistently showed vigorous membrane responses to both alpha- and beta-adrenergic agonists, suggesting that cytoplasmic components essential for the thermogenic response are lost in whole-cell experiments. The membrane responses to adrenergic stimulation varied from cell to cell but were consistent for a given cell. Responses to bath-applied norepinephrine in voltage-clamped cells had three possible components: (a) a fast transient inward current, (b) a slower outward current carried by K+ that often oscillated in amplitude, and (c) a sustained inward current largely by Na+. The fast inward and outward currents were activated by alpha-adrenergic agonists while the slow inward current was mediated by beta-adrenergic agonists. Oscillating outward currents were the most frequently seen response to norepinephrine stimulation. Activation of this current, termed IK,NE, was independent of voltage and seemed to be carried by Ca2(+)-activated K channels since the current oscillated in amplitude at constant membrane potential and gradually decreased when the cells were bathed with calcium-free external solution. IK,NE had a novel pharmacology in that it could be blocked by 4-aminopyridine, tetraethylammonium, apamin, and charybdotoxin. Both IK,NE and the voltage-gated K channels also present in brown fat (Lucero, M. T., and P. A. Pappone, 1989a. Journal of General Physiology. 93:451-472) may play a role in maintaining cellular homeostasis in the face of the high metabolic activity involved in thermogenesis.

αAl2‐Adrenoceptors mediate the inhibition of cholinergic transmission in parasympathetic ganglia of the rabbit urinary bladder

Intracellular recordings were made from neurons of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder and maintained, in vitro. Bath-application of norepinephrine (NE, 500 nM-5 microM) caused a hyperpolarizing response at the postsynaptic membrane of VPG neurons in a concentration-dependent manner. NE blocked the action potential elicited by an orthodromic stimulation of preganglionic (pelvic) nerve fibers. At a relatively low concentration (5-100 nM), NE depressed the fast excitatory postsynaptic potential (EPSP), without producing the hyperpolarization. NE (100 nM) produced 49 +/- 17% (N = 5) decrease in the amplitude of the fast EPSP. NE did not depress the acetylcholine (ACh) potential produced by iontophoretic application of ACh to the ganglion cells. NE did not affect the amplitude of the miniature EPSP, while it reduced the frequency of miniature EPSPs. These results suggest that NE inhibits the nicotinic transmission in the rabbit VPG, probably reducing the ACh release from presynaptic nerve terminals. Epinephrine (1 microM) was more potent than NE (1 microM) in producing the hyperpolarization as well as the blockade of the fast EPSP amplitude. Isoproterenol was ineffective as an agonist for these inhibitory adrenoceptors. Clonidine mimicked the effect of NE on the fast EPSP. Yohimbine and idazoxan antagonized both the inhibition of the fast EPSP and the hyperpolarization produced by NE. These results suggest that alpha 2-adrenoceptors are responsible for the inhibition of the neuronal activity in parasympathetic ganglia of the rabbit urinary bladder. Immunohistochemical study demonstrated the presence of tyrosine hydroxylase (TH)-labelled neuronal elements in the VPG. They were a small proportion of principal neurons, their dendrites, and many varicose fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

A role for N-methyl-D-aspartate receptors in norepinephrine-induced long-lasting potentiation in the dentate gyrus

Mechanisms of action of norepinephrine (NE) on dentate gyrus granule cells were studied in rat hippocampal slices using extra- and intracellular recordings and measurements of stimulus and amino acid-induced changes in extracellular Ca2+ and K+ concentration. Bath application of NE (10-50 microM) induced long-lasting potentiation of perforant path evoked potentials, and markedly enhanced high-frequency stimulus-induced Ca2+ influx and K+ efflux, actions blocked by beta-receptor antagonists and mimicked by beta agonists. Enhanced Ca2+ influx was primarily postsynaptic, since presynaptic delta [Ca2+]o in the stratum moleculare synaptic field was not altered by NE. Interestingly, the potentiation of both ionic fluxes and evoked population potentials were antagonized by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). Furthermore, NE selectively enhanced the delta [Ca2+]o delta [K+]o and extracellular slow negative field potentials elicited by iontophoretically applied NMDA, but not those induced by the excitatory amino acid quisqualate. These results suggest that granule cell influx of Ca2+ through NMDA ionophores is enhanced by NE via beta-receptor activation. In intracellular recordings, NE depolarized granule cells (4.8 +/- 1.1 mV), and increased input resistance (RN) by 34 +/- 6.5%. These actions were also blocked by either the beta-antagonist propranolol or specific beta 1-blocker metoprolol. Moreover, the depolarization and RN increase persisted for long periods (93 +/- 12 min) after NE washout. In contrast, while NE, in the presence of APV, still depolarized granule cells and increased RN, APV made these actions quickly reversible upon NE washout (16 +/- 9 min). This suggested that NE induction of long-term, but not short-term, plasticity in the dentate gyrus requires NMDA receptor activation. NE may be enhancing granule cell firing by some combination of blockade on the late Ca2+-activated K+ conductance and depolarization of granule cells, both actions that can bring granule cells into a voltage range where NMDA receptors are more easily activated. Furthermore, NE also elicited activity-independent long-lasting depolarization and RN increases, which required functional NMDA receptors to persist.

Voltage-gated potassium channels in brown fat cells.

We studied the membrane currents of isolated cultured brown fat cells from neonatal rats using whole-cell and single-channel voltage-clamp recording. All brown fat cells that were recorded from had voltage-gated K currents as their predominant membrane current. No inward currents were seen in these experiments. The K currents of brown fat cells resemble the delayed rectifier currents of nerve and muscle cells. The channels were highly selective for K+, showing a 58-mV change in reversal potential for a 10-fold change in the external [K+]. Their selectivity was typical for K channels, with relative permeabilities of K+ greater than Rb+ greater than NH+4 much greater than Cs+, Na+. The K currents in brown adipocytes activated with a sigmoidal delay after depolarizations to membrane potentials positive to -50 mV. Activation was half maximal at a potential of -28 mV and did not require the presence of significant concentrations of internal calcium. Maximal voltage-activated K conductance averaged 20 nS in high external K+ solutions. The K currents inactivated slowly with sustained depolarization with time constants for the inactivation process on the order of hundreds of milliseconds to tens of seconds. The K channels had an average single-channel conductance of 9 pS and a channel density of approximately 1,000 channels/cell. The K current was blocked by tetraethylammonium or 4-aminopyridine with half maximal block occurring at concentrations of 1-2 mM for either blocker. K currents were unaffected by two blockers of Ca2+-activated K channels, charybdotoxin and apamin. Bath-applied norepinephrine did not affect the K currents or other membrane currents under our experimental conditions. These properties of the K channels indicate that they could produce an increase in the K+ permeability of the brown fat cell membrane during the depolarization that accompanies norepinephrine-stimulated thermogenesis, but that they do not contribute directly to the norepinephrine-induced depolarization.

Membrane properties, response to amines and to tetanic stimulation of hippocampal neurons in the genetically epileptic mutant mouse tottering.

The petit-mal seizures of the "tottering" mutant mouse (tg) have been attributed to an exaggerated noradrenergic projection from locus coeruleus to the telencephalon (Noebels 1984). In order to investigate the possible epileptogenic mechanisms involved, we have compared hippocampal slices from epileptic (tg/tg) and phenotypically healthy (tg/+) mice. Resting potentials, action potentials and afterpotentials, membrane impedances and time constants were not significantly different in 11 neurons from each group. Bath application of noradrenaline, isoproterenol and histamine or a transient exposure to Mg++-free medium caused a long lasting increase in extracellularly recorded population spikes induced in CA1 by electrical stimulation of stratum radiatum. Isoproterenol blocked the calcium dependent afterhyperpolarization and accommodation of firing. Tetanization of afferent fibres evoked post-tetanic potentiation and long-term potentiation. All these results are qualitatively similar to those previously described in rats and guinea pigs and have revealed no significant difference between tg/tg and tg/+ mice.

Norepinephrine enhances stimulus-evoked calcium and potassium concentration changes in dentate granule cell layer

Changes in extracellular Ca 2+ and K + concentrations were measured in the dentate gyrus with ion-selective/reference electrodes during high-frequency perforant path stimulation. Bath application of norepinephrine (NE, 50 μM) markedly enhanced both evoked decreases in extracellular calcium and increases in extracellular potassium concentration. These effects of NE were observed in the granule cell layer (stratum granulosum), but not 200 μm away in the dendritic layer (stratum moleculare). The β-antagonist propranolol (1 μM) completely blocked the NE-induced enhancement of Ca 2+ signals in the dentate. In contrast to the dentate, NE did not enhance evoked Ca 2+ of K + concentration changes in the CA1 pyramidal cell layer. These results indicate that NE markedly enhanced both Ca 2+ and K + fluxes, probably by a β-receptor-mediated mechanism, in the dentate gyrus during high-frequency stimulation of a type able to elicit long-term potentition (LTP). These increases may underly the action of NE in modulating LTP in the dentate gyrus.