Activation Of CA1 Pyramidal Neurons Research Articles

Ensemble Patterns of Hippocampal CA3-CA1 Neurons during Sharp Wave–Associated Population Events

Transfer of neuronal patterns from the CA3 to CA1 region was studied by simultaneous recording of neuronal ensembles in the behaving rat. A nonlinear interaction among pyramidal neurons was observed during sharp wave (SPW)–related population bursts, with stronger synchrony associated with more widespread spatial coherence. SPW bursts emerged in the CA3a-b subregions and spread to CA3c before invading the CA1 area. Synchronous discharge of >10% of the CA3 within a 100 ms window was required to exert a detectable influence on CA1 pyramidal cells. Activity of some CA3 pyramidal neurons differentially predicted the ripple-related discharge of circumscribed groups of CA1 pyramidal cells. We suggest that, in SPW behavioral state, the coherent discharge of a small group of CA3 cells is the primary cause of spiking activity in CA1 pyramidal neurons.

Effects of serotonin on induced epileptiform activity in CA1 pyramidal neurons of genetically epilepsy prone rats

The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported to be caused by abnormalities in several neurotransmitter systems including the serotonergic system. Among the reported abnormalities is a decrease in brain serotonin content. Therefore, we examined the effects of exogenous serotonin on brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed conventional electrophysiological techniques to record from CA1 pyramidal neurons of hippocampi of GEPR-9s. The membrane resting potential and input resistance of the GEPR-9 CA1 pyramidal neurons were not different from those of the Sprague–Dawley rats. Serotonin (20 μM) inhibited the directly and synaptically evoked action potentials in GEPR-9 CA1 neurons, as it did in the Sprague Dawley neurons, but only in some and not all of the neurons tested (blocked the directly evoked potentials in 57% and synaptically evoked potentials in 33.3% of the total neurons). This inhibition was also accompanied by hyperpolarization and reduction of membrane input resistance. In the bicuculline-treated brain slices of the GEPR-9, serotonin inhibited the epileptiform bursts causing concurrent hyperpolarization and reduction in membrane input resistance. The effects of the selective serotonin 5-HT 1A receptor agonist, 8-OH-DPAT (20 μM) on GEPR-9 pyramidal CA1 neurons were similar to those of serotonin, except the magnitude of hyperpolarization and reduction of membrane input resistance were less than those produced by serotonin. We conclude that the apparent decrease in sensitivity of the GEPR-9 CA1 pyramidal neurons to serotonin may represent a deficiency of serotonin 5-HT 1A receptor.

Histochemical study of Ca(2+)-ATPase activity in ischemic CA1 pyramidal neurons in the gerbil hippocampus.

Although cytosolic Ca2+ accumulation plays a pivotal role in delayed neuronal death, there have been no investigations on the role of the cellular Ca2+ export system in this novel phenomenon. To clarify the function of the Ca(2+)-ATPase activity of CA1 pyramidal neurons was investigated ultracytochemically in normal and ischemic gerbil hippocampus. To correlate enzyme activity with delayed neuronal death, histochemical detection was performed at various recirculation times after 5 min of ischemia produced by occlusion of the bilateral carotid arteries. At 10 min after ischemia, CA1 pyramidal neurons showed weak Ca(2+)-ATPase activity. Although enzyme activity had almost fully recovered 2 h after ischemia, it was reduced again 6 h after ischemia. Thereafter, Ca(2+)-ATPase activity on the plasma membrane of CA1 pyramidal neurons decreased progressively, losing its localization on day 3. On day 4 following ischemia, reaction products were diffusely scattered throughout the whole cell body. Our results indicate that, after once having recovered from ischemic damage, severe disturbance of the membrane Ca2+ export system proceeds from the early stage of delayed neuronal death and disturbs the re-export of accumulated cytosolic Ca2+, which might contribute to delayed neuronal death. Occult disruption of Ca2+ homeostasis seems to occur from an extremely early stage of delayed neuronal death in CA1 pyramidal cells.

Excessive intracellular Ca2+ inhibits glutamate-induced Na(+)-K+ pump activation in rat hippocampal neurons.

1. The effects of increased intracellular Ca2+ concentration ([Ca2+]i) on Na(+)-K+ pump activity in CA1 pyramidal neurons of rat hippocampal slices were investigated. The postglutamate hyperpolarization (PGH), which follows glutamate (GLU)-induced depolarization (GD), was used as an index of Na(+)-K+ pump activity, as was a ratio of PGH area to the preceding GD area (PGH ratio). 2. Perfusion of slices with saline containing Ca2+ ionophore (A23187, 10 microM) inhibited the PGH without producing apparent signs of cell deterioration. A 60-100% (85 +/- 15%, mean +/- SD) reduction in the PGH ratio occurred after 20-50 min of A23187 superfusion in 12 of 18 neurons tested. Complete abolition of the PGH occurred in 8 of these 12 cells exposed to A23187 for 30-120 min. 3. Application of A23187 in Ca(2+)-free/high-Mg2+ solution did not abolish the PGH, although small (less than 50%; 37 +/- 10%) reductions in the PGH ratio were observed after perfusion of 50 min or longer in five neurons tested. 4. Intracellular injection of the Ca2+ chelator bis-(o-amino-phenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 300-400 mM) blocked inhibition of the PGH by A23187. After 50 min of perfusion with Ca2+ ionophore, no reduction of the PGH ratio was observed in five neurons tested. 5. Rundown of the PGH without apparent change in membrane properties was observed in three neurons that were stable for greater than 2-3 h, allowing repetitive GLU applications. 6. Block of the PGH produced by a Na(+)-K(+)-adenosinetriphosphatase (ATPase) inhibitor (strophanthidin) prolonged the duration of GDs because of a delay in repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal development of electrogenic sodium pump activity in rat hippocampal pyramidal neurons

We assessed the development of electrogenic sodium pump (Na + pump) activity in CA1 pyramidal neurons of rat hippocampal slices by studying the prolonged hyperpolarization which follows glutamate-induced depolarization (postglutamate hyperpolarization or PGH) at different postnatal ages. We also examined the development of membrane-bound enzyme in the hippocampal CA1 subfield with light microscopic immunocytochemistry and an antiserum against Na +,K +-ATPase. The PGH, which has previously been shown to be due to activation of an electrogenic Na + pump in adult hippocampal CA1 neurons, was eliminated by strophanthidin, a Na +,K +-ATPase inhibitor, at all ages. It was unaffected by several potassium channel blockers, an intracellular calcium chelator, intracellular Cl − injection or tetrodotoxin (TTX) perfusion. The PGH thus appeared to be independent of K + and C1 − conductances and produced by an electrogenic Na + pump in adult and immature animals activated in large part by entry of Na + through the glutamate receptor-channel complex. The size (integrated area) of the PGH was directly proportional to the area of preceding glutamate-induced depolarization (GD) and relatively voltage independent. Similar GDs could be elicited from postnatal day (P) 7 to P ⩾ 35, however, only very small PGHs were produced in neurons from P7–11 animals. A ratio of PGH area to GD area (PGH ratio) was calculated for each neuron and used to compare Na + pump activity at different ages. There was a significant increase in the mean PGH ratio with age when P7–11, P21–25 and P35–39 groups were compared. Na + pump activity estimated from the PGH ratio is very low in the first postnatal week but develops gradually over the first 5 weeks of life. Immunostaining for Na +,K +-ATPase in adult rat hippocampi revealed a punctate reaction product surrounding pyramidal cell bodies, whereas the staining was uniform along plasmalemma of dendrites in striatum radiatum and stratum oriens. By contrast, only minimum staining was present surrounding cell bodies and dendrites of P7 hippocampi and staining in striatum pyramidale was not punctate at this age. Na +,K +-ATPase activity estimated grossly from immunocytochemical staining is very low in the first from natal week, increases during the first 5 weeks and develops a characteristic focal localization. These results suggest that Na +,K +-ATPase levels in hippocampal CA1 pyramidal neurons are low and insufficient to allow substantial activity of the Na + pump in the first postnatal week, with gradual attainment of adult functional levels over subsequent weeks. The period of development of the PGH is comparable with that found using immunocytochemical staining for Na +,K +-ATPase. Lower levels of electrogenic Na + pump activity at early stages of development could be one factor contributing to the increased susceptibility of immature hippocampus to ictal discharges associated with prolonged membrane depolarization.

Hippocampal neuronal responsiveness to different neurotransmitters in the adult rat after neonatal interference with noradrenaline transmission

In order to test the functional significance of noradrenergic neurotransmission for brain maturation, rat pups were injected daily with clonidine from 8–21 days of postnatal life. In adulthood, single cell responses to microiontophoretically applied neurotransmitters were studied in different layers of the hippocampus. No significant differences were found in neuronal responsiveness to glutamate, GABA, or acetylcholine in the hippocampus of clonidine-treated rats as compared with age-matched controls. However, there was a significantly stronger depression of glutamate-evoked activity of CA1 pyramidal neurons by noradrenaline in the clonidine-treated rats.

Perforant pathway activation of hippocampal CA1 stratum pyramidale neurons: Electrophysiological evidence for a direct pathway

Electrophysiological techniques were used to investigate the effect of stimulating the perforant pathway (PP) on pyramidal neurons in the CA1 region of the hippocampal slice. Stimulation of the PP evoked both field potentials and single unit discharges in the pyramidal cell layer of the CA1 region. Several lines of experimental evidence suggest that the CA1 response does not involve granule or CA3 neurons: (i) movement of the recording electrode in the CA1 region away from the site of stimulation in the PP and closer to the CA3 region increased the latency of the evoked potential; (ii) the sum of latencies of the individual pathways in a trisynaptic circuit - from the PP to granule cells to CA3 neurons to CA1 neurons - was 2-3 times longer than the latency of the PP evoked response recorded in the CA1 region: (iii) lesioning the mossy fiber pathway or excising the CA3 region did not inhibit the CA1 response to PP stimulation. Other experimental results suggest that the PP activation of CA1 pyramidal neurons involves a direct synaptic pathway: (i) PP stimulation evoked potentials with similar latencies in the dentate gyrus and the CA1 region; (ii) the CA1 response was abolished in a Krebs' solution containing low calcium/high magnesium; (iii) excising a portion of the CA1 region between the stimulating electrode in the PP and the CA1 recording electrode, but sparing the PP, did not abolish the CA1 response; (iv) electrolytic lesions of the PP abolished the CA1 response to PP stimulation, but did not affect the CA1 response to stimulation of the CA3 region. The data suggest that fibers in the PP make direct synaptic connection with pyramidal neurons in the CA1 region of the hippocampus.

Dendritic Mechanisms Underlying Penicillin-Induced Epileptiform Activity

The action of penicillin on synaptically evoked dendritic activity was examined with the use of hippocampal slice preparations. Orthodormic activation of CA1 pyramidal neurons produced an excitatory-inhibitory postsynaptic potential sequence recorded intracellularly in the dendrites. Treatment with penicillin resulted in the appearance of spontaneous and synaptically evoked multipeaked field potentials and associated depolarization shifts and spike burst generation in CA1 cells. Intracellular recordings revealed that penicillin produced no detectable change in passive membrane properties of the postsynaptic dendrites. However, the inhibitory postsynaptic potential was suppressed by penicillin, resulting in the release of intrinsic dendritic burst firing during synaptic activation. These findings emphasize the role of normal patterns of dendritic burst generation in the production of intense neuronal discharge during penicillin-induced epileptiform activities.