Developmental changes in membrane properties and postsynaptic currents of granule cells in rat dentate gyrus

1996 ◽  
Vol 76 (2) ◽  
pp. 1074-1088 ◽  
Author(s):  
Y. B. Liu ◽  
P. A. Lio ◽  
J. F. Pasternak ◽  
B. L. Trommer

1. Whole cell patch-clamp recordings were used to study dentate gyrus granule cells in hippocampal slices from juvenile rats (postnatal days 8-32). Membrane properties were measured with the use of current-clamp recordings and were correlated with the morphology of a subgroup of neurons filled with biocytin. The components of the postsynaptic currents (PSCs) induced by medial perforant path stimulation were characterized with the use of specific receptor antagonists in voltage-clamp recordings. 2. Granule cells located in the middle third of the superior blade of stratum granulosum from the rostral third of hippocampus were divided into three groups according to their input resistance (IR). Neurons with low IR (206 +/- 182 M omega, mean +/- SD) had hyperpolarized resting membrane potentials (-82 +/- 7 mV) and high-amplitude action potentials (108 +/- 23 mV). Neurons were high IR (1,259 +/- 204 M omega) had more depolarized resting membrane potentials (-54 +/- 6 mV) and lower-amplitude action potentials (71 +/- 10 mV). Neurons with intermediate IR (619 +/- 166 M omega) also had intermediate resting membrane potentials (-63 +/- 7 mV) and action potential amplitudes (86 +/- 14 mV). Low-IR neurons became increasingly prevalent with advancing postnatal age, but neurons from each group could be found throughout the entire period under study. 3. Morphological studies of low-IR neurons revealed an extensive dendritic arborization that traversed the entire molecular layer and was characteristic of mature granule cells. High-IR cells had smaller somata and short, simple dendritic arborization that incompletely penetrated the molecular layer and were classified as immature. Intermediate-IR cells had morphological features of intermediate maturity. 4. The initial phase of the PSC evoked at -80 mV was a fast inward current that was comparable with respect to latency to peak, latency to onset, and 10-90% rise time in neurons of all maturities held at -80 mV. This current was 6-cyano-7-nitroquinoxaline-2,3-dione sensitive. 5. The decay phases of PSCs at -80 mV varied with neuronal maturity. Mature neurons had monoexponential decays (tau = 8.9 +/- 3.6). Intermediate and immature neurons had prominent later inward currents that resulted in slower decays. In the case of the immature neurons, the inward current during the decay phase could be separated from the initial fast inward peak. The later inward currents in intermediate and immature neurons were bicuculline sensitive. 6. With the use of uniform ionic conditions of the extracellular and patch solutions, current-voltage relations and reversal potentials for pharmacologically isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid-A (GABAA) currents were comparable across all cell maturities. Calculated ratios for peak GABAA/NMDA/AMPA currents decreased significantly with maturation as follows: 9.4 +/- 2.9/1.4 +/- 0.5/1.0 for immature cells, 7.2 +/- 2.5/1.5 +/- 0.7O/1.0 for intermediate cells, and 2.0 +/- 1.2/0.9 +/- 0.4/1.0 for mature cells. 7. GABA current was mediated both by polysynaptic activation of interneurons and by direct activation of interneurons with monosynaptic input onto granule cells. The proportional contributions of mono- and polysynaptic GABA to total GABA were comparable across all cell maturities; latency to peak GABA current decreased with increasing cell maturity for both mono- and polysynaptic components. 8. We conclude that PSCs evoked in granule cells by medial perforant path activation in neurons of all maturities consist of both glutamatergic and GABAergic components. PSCS are dominated by GABAergic neurotransmission in immature granule cells, and the contribution of glutamatergic neurotransmission increases with neuronal maturation. The greater ratio of peak GABAA to glutamate currents and the longer time interval between their respective peaks combine to produce a distinctive PSC shape

Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.


1995 ◽  
Vol 74 (4) ◽  
pp. 1485-1497 ◽  
Author(s):  
J. Schmidt ◽  
S. Gramoll ◽  
R. L. Calabrese

1. The effects of Phe-Met-Arg-Phe (FMRF)amide (10(-6) M) on membrane properties of heart interneurons in the third, fourth, and fifth segmental ganglia [HN(3), HN(4), and HN(5) cells, respectively] of the leech were studied using discontinuous current-clamp and single-electrode voltage-clamp techniques. FMRFamide was focally applied onto the soma of the cell under investigation. 2. Application of FMRFamide depolarized HN(3) and HN(4) cells by evoking an inward current. These responses were subject to pronounced desensitization. The inward currents evoked by application of FMRFamide were associated with an increase in membrane conductance and appeared to be voltage dependent. Currents were enhanced at more depolarized potentials. 3. The responsiveness of the HN(3) and HN(4) cells was not affected when the Ca2+ concentration in the bath saline was reduced from normal (1.8 mM) to 0.1 mM. The depolarizing response on application of FMRFamide was blocked when Co2+ was substituted for Ca2+. 4. HN(3) and HN(4) cells did not respond to FMRFamide application in Na(+)-free solution. Inward currents were largely reduced when bath saline with 30% of the normal Na+ concentration was used. When Li+ was substituted for Na+ in the saline, application of FMRFamide still evoked depolarizing responses in HN(3) and HN(4) cells. 5. We conclude that focal application of FMRFamide onto the somata of HN(3) and HN(4) cells evokes a voltage-dependent inward current, carried largely by Na+. 6. Focal application of FMRFamide onto somata of HN(5) cells hyperpolarized these cells by activating a voltage-dependent outward current. 7. HN(5) cells were loaded with Cl- until inhibitory postsynaptic potentials carried by Cl- reversed. Cl(-)-loaded cells still responded with a hyperpolarization when FMRFamide was applied onto their somata. Therefore the outward current evoked by FMRFamide appears to be mediated by a K+ conductance increase. 8. Application of FMRFamide onto the somata of HN(5) cells enhanced outward currents that were evoked by depolarizing voltage steps from a holding potential of -45 mV. 9. We conclude that the hyperpolarizing response of HN(5) cells to focal application of FMRFamide onto their somata is the result of an up-regulation of a voltage-dependent K+ current.


1994 ◽  
Vol 71 (6) ◽  
pp. 2217-2235 ◽  
Author(s):  
S. Williams ◽  
D. D. Samulack ◽  
C. Beaulieu ◽  
J. C. LaCaille

1. The membrane properties and synaptic inputs of interneurons, located at the stratum (s.) lacunosum-moleculare and radiatum border (L-M) of the CA1 region, were examined with the use of current-clamp whole-cell recordings in rat hippocampal slices. 2. Biocytin-labeled L-M interneurons had nonpyramidal somata and aspinous, often beaded, dendrites that arborized in s. lacunosum-moleculare and radiatum, sometimes as far as s. moleculare of the dentate gyrus. Their axon coursed and branched in s. lacunosum-moleculare and radiatum. Axon collaterals were also observed traversing the hippocampal fissure and arborizing in s. moleculare of the dentate gyrus and s. radiatum of the CA3 region. 3. Several membrane properties of interneurons were typically nonpyramidal: they had large input resistances, short-duration action potentials followed by prominent fast afterhyperpolarizations, and responded to hyperpolarizing current pulses with little membrane rectification. L-M interneurons showed significant anodal break responses, and their mean membrane time constant was 33 ms. After-depolarizations elicited by subthreshold depolarizing current pulses were larger in amplitude and decayed more slowly at depolarized than hyperpolarized membrane potentials. 4. The majority of L-M interneurons (35 of 49 cells) were silent at resting membrane potentials, whereas other displayed either spontaneous single action potentials (n = 12) or rhythmic bursts (n = 2). The rhythmic bursts were insensitive to the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP-5; 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM), respectively. Both spontaneous single action potentials and burst firing were blocked by membrane hyperpolarization, suggesting that they were intrinsically rather than synaptically generated. 5. L-M interneurons responded with regular sustained firing to depolarizing current pulses at resting membrane potential. However, at more hyperpolarized membrane potentials (near -75 mV), depolarizing current pulses elicited action-potential firing with a delayed onset. This suggests that voltage-sensitive, transient outward currents may be activated in L-M interneurons from hyperpolarized membrane potentials. 6. Electrical stimulation of s. radiatum or lacunosum-moleculare elicited predominantly long-duration excitatory postsynaptic potentials (EPSPs; n = 20 cells), or both EPSPs and inhibitory postsynaptic potentials (IPSPs; n = 17 cells). In most L-M interneurons (35/37), with increasing intensities, up to two action potentials were elicited. Occasionally, larger bursts (3–5 action potentials) were observed (n = 2). 7. The multiphasic components of the synaptic responses became more evident when stimulations were repeated at different membrane potentials.(ABSTRACT TRUNCATED AT 400 WORDS)


1991 ◽  
Vol 157 (1) ◽  
pp. 101-122
Author(s):  
WERNER A. WUTTKE ◽  
MICHAEL S. BERRY

1. The giant salivary cells of Haementeria ghilianii are known to produce Ca2+-dependent action potentials and to release their secretory products in response to stimulation of the stomatogastric nerve. In this study, the electrophysiological effects of some putative transmitters were examined by perfusion of the gland and two promising candidates were selected for detailed analysis. 2. Acetylcholine (ACh) was the only substance tested which excited the gland cells. It produced a large, Na+-dependent depolarization that elicited 1–3 action potentials and desensitized to about 24% of its maximal value within 2 min. 3. Carbachol, tetramethylammonium and nicotine elicited similar responses to ACh, whereas choline and pilocarpine had negligible effects. 4. The ACh response was completely blocked by d-tubocurarine and strychnine, and was reduced by tetraethylammonium, hexamethonium and atropine. The receptors, therefore, cannot be clearly distinguished as nicotinic or muscarinic. 5. ACh did not elicit secretion, but this does not necessarily preclude it from acting as a neuroglandular transmitter. 6. 5-Hydroxytryptamine (5-HT) was the only transmitter candidate that elicited secretion, though it did not excite the gland cells. 7. 5-HT produced a subthreshold depolarization and an increase in input resistance. Action potentials, elicited by depolarizing pulses, were increased in amplitude and duration, and showed greatly reduced adaptation. 8. 5-HT potentiated the net inward current, evoked by subthreshold depolarizing pulses, by reducing outward K+ current. The inward current, carried by Ca2+, was not directly affected. In addition, 5-HT increased an inwardly rectifying current, carried by Na+ and K+. All the effects of 5-HT tended to increase cell excitability. 9. Salivary cell responses to 5-HT were reversibly antagonised by methysergide. 10. Responses to ACh or 5-HT were not mimicked by 3′, 5′-cyclic guanosine monophosphate, which greatly reduced spike amplitude and excitability. The effects were specific to the 3′, 5′ form; 2′, 3′-cyclic GMP had no effect. Cyclic GMP dramatically reduced the duration of action potentials that had been artificially prolonged by TEA+ or removal of external Ca2+. 11. Cyclic 3′, 5′-adenosine monophosphate and its dibutyryl derivative had little effect on membrane properties. 8-Bromo-cyclic AMP, however, mimicked all the effects of 5-HT. It is thought that 5-HT may exert its actions via cyclic AMP. 12. The possible role of 5-HT in salivary secretion is discussed.


2003 ◽  
Vol 90 (4) ◽  
pp. 2358-2366 ◽  
Author(s):  
Laura Lee Colgin ◽  
Enikö A. Kramár ◽  
Christine M. Gall ◽  
Gary Lynch

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.


2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.


1996 ◽  
Vol 76 (1) ◽  
pp. 601-616 ◽  
Author(s):  
M. B. Jackson ◽  
H. E. Scharfman

1. Microelectrode recording and fluorescence measurement with voltage-sensitive dyes were employed in horizontal hippocampal slices from rat to investigate responses in the dentate gyrus to molecular layer and hilar stimulation. 2. Both field potential and dye fluorescence measurement revealed that electrical stimulation of the molecular layer produced strong excitation throughout large regions of the dentate gyrus at considerable distances from the site of stimulation. 3. Treatment of slices with the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the outer and middle molecular layers corresponding to action potentials in axons, presumably belonging to the perforant path. The spread of these axonal signals away from the site of stimulation was far less extensive than the spread of control signals through the same regions before blockade of excitatory synapses. Large control responses could be seen in regions distant from the stimulation site where the axonal signals were not detectable. A lack of correlation between control signals and axonal signals revealed by DNQX and APV supports the hypothesis that responses in distal regions of the molecular layer were not dependent on perforant path axons. 4. The perforant path was cut by producing a lesion in the outer two-thirds of the molecular layer. Both dye fluorescence and microelectrode recording showed that stimulation on one side of the lesion could produce signals on the same side as well as across the lesion. The lesion did not block the spread of excitation through the molecular layer. Across the lesion from the site of stimulation, negative-going field potentials were observed to peak in the inner molecular layer, which is the major field of projection of hilar mossy cells. 5. Electrical stimulation in the hilus adjacent to the granule cell layer evoked dye fluorescence responses in the molecular layer. Stimulation at this site evoked negative-going field potentials that peaked in the inner molecular layer. These signals were sensitive to excitatory amino acid receptor antagonists but not to gamma-aminobutyric acid-A (GABAA) receptor antagonists. 6. Activation of excitatory amino acid receptors in the hilus by focal application of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) elicited negative-going field potentials in the granule cell layer and depolarization of granule cells. Field potentials were blocked by tetrodotoxin (TTX), indicating that they were not caused by direct activation of receptors on granule cells, but rather by synapses from hilar neurons on granule cells. 7. These results taken together with previous studies of hilar mossy cells suggest a fundamental circuit consisting of granule cells exciting hilar mossy cells, which then excite more granule cells. This circuit provides positive feedback and can be considered a form of "recurrent excitation" unique to the dentate gyrus. The robustness of this circuit in hippocampal slices under control conditions suggest that mossy cell excitation of granule cells could play an important role in the normal activity of the hippocampus, and, when inhibition is compromised, this circuit could contribute to the generation and spread of seizures.


1998 ◽  
Vol 79 (1) ◽  
pp. 496-499 ◽  
Author(s):  
Elhoucine Messaoudi ◽  
Kjetil Bårdsen ◽  
Bolek Srebro ◽  
Clive R. Bramham

Messaoudi, Elhoucine, Kjetil Bårdsen, Bolek Srebro, and Clive R. Bramham. Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentategyrus. J. Neurophysiol. 79: 496–499, 1998. The effect of acuteintrahippocampal infusion of brain-derived neurotrophic factor (BDNF) on synaptic transmission in the dentate gyrus was investigated in urethan-anesthetized rats. Medial perforant path-evoked field potentials were recorded in the dentate hilus and BDNF-containing buffer was infused (4 μl, 25 min) immediately above the dentate molecular layer. BDNF led to a slowly developing increase of the field excitatory postsynaptic potential (fEPSP) slope and population spike amplitude. The potentiation either reached a plateau level at ∼2 h after BDNF infusion or continued to increase for the duration of experiment; the longest time point recorded was 10 h. Mean increases at 4 h after BDNF infusion were 62.2 and 224% for the fEPSP slope and population spike, respectively. No changes in responses were observed in controls receiving buffer medium only or buffer containing cytochrome C. BDNF-induced potentiation developed in the absence of epileptiform activity in the hippocampal electroencephalogram or changes in recurrent inhibition on granule cells as assessed by paired-pulse inhibition of the population spike. We conclude that exogenous BDNF induces a lasting potentiation of synaptic efficacy in the dentate gyrus of anesthetized adult rats.


1999 ◽  
Vol 77 (6) ◽  
pp. 383-397
Author(s):  
Qi-Ying Liu ◽  
Mario Vassalle

The role of Na-Ca exchange in the membrane potential changes caused by repetitive activity ("drive") was studied in guinea pig single ventricular myocytes exposed to different [Ca2+]o. The following results were obtained. (i) In 5.4 mM [Ca2+]o, the action potentials (APs) gradually shortened during drive, and the outward current during a train of depolarizing voltage clamp steps gradually increased. (ii) The APs shortened more and were followed by a decaying voltage tail during drive in the presence of 5 mM caffeine; the outward current became larger and there was an inward tail current on repolarization during a train of depolarizing steps. (iii) These effects outlasted drive so that immediately after a train of APs, currents were already bigger and, after a train of steps, APs were already shorter. (iv) In 0.54 mM [Ca2+]o, the above effects were much smaller. (v) In high [Ca2+]o APs were shorter and outward currents larger than in low [Ca2+]o. (vi) In 10.8 mM [Ca2+]o, both outward and inward currents during long steps were exaggerated by prior drive, even with steps (+80 and +120 mV) at which there was no apparent inward current identifiable as ICa. (vii) In 0.54 mM [Ca2+]o, the time-dependent outward current was small and prior drive slightly increased it. (viii) During long steps, caffeine markedly increased outward and inward tail currents, and these effects were greatly decreased by low [Ca2+]o. (ix) After drive in the presence of caffeine, Ni2+ decreased the outward and inward tail currents. It is concluded that in the presence of high [Ca2+]o drive activates outward and inward Na-Ca exchange currents. During drive, the outward current participates in the plateau shortening and the inward tail current in the voltage tail after the action potential.Key words: ventricular myocytes, repetitive activity, outward and inward Na-Ca exchange currents, caffeine, nickel.


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