Electrophysiological Properties Of Hippocampal Neurons Research Articles

Intriguing Roles of Hippocampus-Synthesized 17β-Estradiol in the Modulation of Hippocampal Synaptic Plasticity

Accumulated studies have shown that 17β-estradiol (E2) can be de novo synthesized in the hippocampus, and its role in the regulation of hippocampal synaptic plasticity, which is the basis of learning and memory, has long been exploring. Steroidogenic enzymes (e.g., aromatase) that are essential to the hippocampus-synthesized synthesis of E2 have been detected in the hippocampus. Inhibition of E2 synthesis by aromatase inhibitors significantly reduces the density of hippocampal spine synapses, levels of some synaptic proteins such as spinopholin and synaptophysin. Moreover, the electrophysiological properties of hippocampal neurons are also changed in response to this inhibition. The influences of gonadal and hippocampal E2 on synaptic plasticity may exist some differences, since some reports showed that gonadal (or circulating) estrogens have no obvious effects in the modulation of hippocampal synaptic proteins as evidenced in some ovariectomized animals and postmenopausal women who suffered from Alzheimer's disease (AD). These evidences leads to a hypothesis that hippocampal E2 may play a more important role in modulation of synaptic plasticity than gonadal E2. The signaling pathways, whereby hippocampal E2 modulates synaptic plasticity, insist of classical chronic genomic pathway and rapid nongenomic pathway, which mediated by nonnuclear estrogen receptor (GPER) and/or nuclear or nonnuclear estrogen receptors, which require coactivators for their transcription activity. Among which steroid receptor coactivator-1 (SRC-1) is the predominant coactivator p160 family members in the brain. Several clues have shown that SRC-1 is expressed in hippocampus and is highly correlated with some key synaptic proteins developmentally or after orchidectomy but not ovariectomy, indicating SRC-1 may be regulated by hippocampus-synthesized E2 and profoundly involved in the mediation of hippocampal E2 regulation of hippocampal synaptic plasticity. Further studies about the exact roles of hippocampus-synthesized E2 and therefore SRC-1 are urgently needed in order to facilitate our understanding of hippocampal E2, which will be very important to the development of novel strategies of estrogen replacement therapy against neurodegenerative deficits such as Alzheimer's disease (AD).

The MeCP2‐null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability

Rett syndrome is an autism-spectrum disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2). While subtle decreases in synaptic plasticity have been detected within cortical and hippocampal neurons of Mecp2-null mice, only minimal information exists regarding how the loss of MeCP2 affects network activity in the brain. To address this issue, we compared the intrinsic network activities of Mecp2-null hippocampal slices derived from symptomatic mice to wild-type slices. Extracellular and whole-cell patch recordings revealed that although spontaneous, IPSP-based rhythmic activity is present in Mecp2-null slices; its frequency is significantly reduced from wild-type. This reduction was not associated with alterations in the gross electrophysiological properties of hippocampal neurons, but was associated with a decreased level of spontaneous glutamate receptor-mediated synaptic currents in hippocampal CA3 neurons. Paradoxically, however, repetitive sharp wave-like discharges were readily induced in the Mecp2-null hippocampal slices by a brief train of high-frequency stimulation commonly used to establish long-term potentiation at wild-type slices. Taken together, our data indicate that the Mecp2-null hippocampal CA3 circuit has diminished basal inhibitory rhythmic activity, which in turn renders the circuitry prone to hyperexcitability.

Estrogen Regulates the Development of Brain-Derived Neurotrophic Factor mRNA and Protein in the Rat Hippocampus

During development, estrogen has a variety of effects on morphological and electrophysiological properties of hippocampal neurons. Brain-derived neurotrophic factor (BDNF) also plays an important role in the survival and differentiation of neurons during development. We examined the effects of gonadectomy with and without estrogen replacement on the mRNA and protein of BDNF and its receptor, trkB, during early postnatal development of the rat hippocampus. We used immunocytochemistry to demonstrate that estrogen receptor α (ERα) and BDNF were localized to the same cells within the developing hippocampus. BDNF and ERα were colocalized in pyramidal cells of the CA3 subregion and to a lesser extent in CA1. To determine whether BDNF mRNA was regulated by estrogen during development, we gonadectomized male rat pups at postnatal day 0 (P0) and examined mRNA and protein levels from P0 to P25 using real-time reverse transcription-PCR and Western blot analysis. After gonadectomy, BDNF mRNA levels are significantly reduced on P7, but after treatment of gonadectomized animals with estradiol benzoate on P0, levels at all ages were similar to those in intact animals. BDNF mRNA changes after gonadectomy are accompanied by an increase in the levels of BDNF protein, which were reduced by estrogen treatment at P0. We also examined the effect of postnatal estrogen treatment on trkB. There were no significant changes in trkB mRNA or protein in gonadectomized or estrogen-replaced animals. These results suggest that a direct interaction may exist between ERα and BDNF to alter hippocampal physiology during development in the rat.

Estrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus.

During development, estrogen has a variety of effects on morphological and electrophysiological properties of hippocampal neurons. Brain-derived neurotrophic factor (BDNF) also plays an important role in the survival and differentiation of neurons during development. We examined the effects of gonadectomy with and without estrogen replacement on the mRNA and protein of BDNF and its receptor, trkB, during early postnatal development of the rat hippocampus. We used immunocytochemistry to demonstrate that estrogen receptor alpha (ERalpha) and BDNF were localized to the same cells within the developing hippocampus. BDNF and ERalpha were colocalized in pyramidal cells of the CA3 subregion and to a lesser extent in CA1. To determine whether BDNF mRNA was regulated by estrogen during development, we gonadectomized male rat pups at postnatal day 0 (P0) and examined mRNA and protein levels from P0 to P25 using real-time reverse transcription-PCR and Western blot analysis. After gonadectomy, BDNF mRNA levels are significantly reduced on P7, but after treatment of gonadectomized animals with estradiol benzoate on P0, levels at all ages were similar to those in intact animals. BDNF mRNA changes after gonadectomy are accompanied by an increase in the levels of BDNF protein, which were reduced by estrogen treatment at P0. We also examined the effect of postnatal estrogen treatment on trkB. There were no significant changes in trkB mRNA or protein in gonadectomized or estrogen-replaced animals. These results suggest that a direct interaction may exist between ERalpha and BDNF to alter hippocampal physiology during development in the rat.

Localization of estrogen receptor alpha (ERα) in pyramidal neurons of the developing rat hippocampus

During development, estrogen has a variety of effects on morphological, biochemical and electrophysiological properties of hippocampal neurons. Correspondingly, estrogen receptor (ER) binding and mRNA increase transiently in the developing hippocampus. In this study, we used immunocytochemistry to determine the localization of the ERα subtype in the developing rat hippocampus. Nuclear staining was present in pyramidal cells and some interneurons of the CA1 and CA3 regions of the developing rat hippocampus. Little or no immunoreactivity was observed in postnatal day (P)0 animals (day of birth=P0), however, beginning on P4, ERα-immunoreactivity (ERα-ir) was visible and reached maximal levels by P10. These levels subsequently declined to low levels so that by P15, levels approximated those of adult females. Western blot analysis confirmed that this antibody recognized a 67 kDa protein, characteristic of the full-length ERα protein, in the hippocampus and pituitary. Furthermore, most of the ERα-immunopositive cells in the hippocampus were located in the pyramidal cell layer, and did not co-localize appreciably with γ-aminobutyric acid (GABA) at any age examined. We conclude, based on the immunocytochemical localization of ERα, that the effects of estrogen on biochemistry and morphology of the developing hippocampus may be direct through the ERα subtype in hippocampal pyramidal cells.

Electrophysiological properties of rat hippocampal principal cells are unaltered by prenatal protein malnutrition.

There is growing evidence that prenatal protein malnutrition alters the development of the hippocampal formation in rats (Morgane et al., 1993; Galler et al., 1996; Almeida et al., 1996, for reviews). Little is known, however, of the possible functional consequences of prenatal malnutrition on the physiology of principal cells in the hippocampus. We have addressed this issue by comparing the electrophysiological properties of hippocampal neurons (dentate granule cells and CA1 pyramidal cells) in slices prepared from control and from prenatally protein malnourished adult male and female Sprague-Dawley rats. We found no significant effect of the prenatal protein malnutrition insult upon a number of intrinsic membrane properties measured with whole-cell current clamp recordings, including: resting membrane potential, input resistance, and membrane time constant, or on action potential characteristics such as threshold, amplitude, and/or firing frequency. Additionally, we saw no effect of prenatal malnutrition upon extracellular measures of glutamatergic synaptic transmission such as the presynaptic fiber volley, excitatory postsynaptic potential or population spike amplitude at the perforant path to dentate granule cell synapse or at the Schaffer collateral to CA1 pyramidal cell synapse. In conclusion, we have demonstrated that prenatal protein malnutrition does not result in significant alterations of the cellular physiological properties of these two types of principal neurons in the adult rat hippocampus.

Electrophysiological development of embryonic hippocampal neurons from the rat grown on synthetic thin films

We have studied the electrophysiological properties of hippocampal neurons grown on surfaces of organic thin films formed on glass or silicon substrates and on microelectronic device surfaces in culture. Hippocampal neurons were dissociated from embryonic rats and plated on substrates chemically modified with laminin peptide in a chemically defined medium. The electrophysiological properties of the neurons were studied using patch-clamp amplifier technique. We observed that the neurons grown on these substrates develop resting membrane potentials more negative than −33 mV after 3 days in culture and are able to produce action potentials. More interestingly we found that the neurons when grown on the microelectronic surfaces develop similar electrophysiological characteristics as those on the glass surfaces. Passive electrical properties ( C m=27±5 pF, R m⩾1 G Ω) of the neurons studied by impedance spectroscopy did not change considerably during the first week in culture.

Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology.

A variety of neurological complications has been reported in infants exposed to cocaine during gestation. In the present study, intrinsic cell properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats exposed to saline or cocaine in utero. Synaptic properties of the CA1 pyramidal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intracellular recordings (n = 223) obtained at P10, P15 and P20 in tissue from cocaine- and saline-exposed animals revealed no differences in standard cell properties such as resting membrane potential, input resistance, time constant, and action potential amplitude or duration. Hippocampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippocampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of afterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellular and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocaine-exposed animals, synaptic responses in the CA1 region were characterized by multiple population spike activity and reduced inhibitory postsynaptic potentials. The reduction in fast inhibitory postsynaptic potential conductance was not associated with a change in reversal potential. These results suggest that gestational cocaine exposure induces significant changes in intrinsic and synaptic electrophysiological properties of hippocampal neurons in the developing animal. The cell and synaptic features are consistent with an increase in hippocampal excitability, which may contribute to the neurobehavioral deficits and epileptogenic predisposition reported in this infant population. As such, this in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurological complications associated with maternal cocaine abuse.

Single-channel and whole-cell studies of calcium currents in young and aged rat hippocampal slice neurons

The hippocampal slice preparation has contributed greatly to analysis of the basic neurophysiology of brain neurons. In addition, because traumatic dissociative procedures are not used, the in vitro slice is particularly well suited for studies of electrophysiological properties of hippocampal neurons in young and aged rodent brain. Using the slice, we have previously observed an aging-dependent enhancement of voltage-activated Ca 2+ influx using a combination of intracellular sharp electrode current-clamp and voltage-clamp techniques. The Ca 2+-dependent afterhyperpolarization as well as the Ca 2+ action potential were significantly larger in aged rat neurons. Using the sharp electrode switch clamp method, similar effects were found for high voltage-activated whole-cell Ca 2+ currents. In order to study the mechanistic bases of these aging phenomena at the single-channel level, we have recently focused on recording cell-attached patches from neurons in the partially dissociated hippocampal slice (‘zipper’ slice). This technique, developed by Gray et al. in 1990, subjects slices to a mild enzymatic treatment resulting in the exposure of individual neurons for patch-clamp procedures. Using this technique, we are currently recording single Ca 2+ channel activity in hippocampal slices from 4- to 29-month-old rats.

Variations in electrophysiological properties of hippocampal neurons in different subfields

Intracellular recording were made from hippocampal pyramidal cells (HPCs) in subregions CAla, b, c, CA2 and CA3a, b of the guinea pig hippocampal slice. There were significant differences in the mode of spike discharge at various sites. Most neurons in CA1b and CA3b fired single spikes spontaneously, or during intracellular depolarizing current pulses. HPCs in the CA1a and c, as well as CA2 and CA3a subregions usually had a burst mode of discharge under the same conditions. Basic differences in neuronal properties presumably underlie these varieties of behavior between or within various regions. Specification of the site or subregion of recording is important especially in those experiments where the mode of spike discharge or membrane events in HPCs are important variables.

Afterpotential generation in hippocampal pyramidal cells.

Afterpotential generation in hippocampal pyramidal cells.

Steady-state electrotonic analysis of intracellularly stained hippocampal neurons.

Steady-state electrotonic analysis of intracellularly stained hippocampal neurons.D A Turner, and P A SchwartzkroinD A Turner, and P A SchwartzkroinPublished Online:01 Jul 1980https://doi.org/10.1152/jn.1980.44.1.184MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByConstitutive Ras activity induces hippocampal hypertrophy and remodeling of pyramidal neurons in synRas mice14 June 2004 | Journal of Neuroscience Research, Vol. 77, No. 5Factors determining the efficacy of distal excitatory synapses in rat hippocampal CA1 pyramidal neurones22 September 2004 | The Journal of Physiology, Vol. 507, No. 2Increased dendritic extent in hippocampal CA1 neurons from aged F344 ratsNeurobiology of Aging, Vol. 17, No. 4Denervation-induced dendritic alterations in CA1 pyramidal cells following kainic acid hippocampal lesions in ratsBrain Research, Vol. 652, No. 2Low-threshold calcium current in dendrites of the adult rat hippocampusNeuroscience Letters, Vol. 164, No. 1-2Anatomical and physiological localization of prelabeled grafts in rat hippocampusExperimental Neurology, Vol. 116, No. 2Functional elongation of CA1 hippocampal neurons with aging in Fischer 344 ratsNeurobiology of Aging, Vol. 12, No. 3Selective vulnerability of the hippocampus in brain ischemiaNeuroscience, Vol. 40, No. 3Apical dendritic depolarizations and field interactions evoked by stimulation of afferent inputs to rat hippocampal ca1 pyramidal cellsNeuroscience, Vol. 42, No. 1Differential effect of norepinephrine upon granule cells and interneurons in the dentate gyrusBrain Research, Vol. 488, No. 1-2Electrophysiological characteristics of morphologically identified reticular thalamic neurons from rat slicesNeuroscience, Vol. 27, No. 2The in vitro slice preparation for combined morphological and electrophysiological studies of rat visual cortexNeuroscience Research, Vol. 6, No. 1Multisite hippocampal slice recording and stimulation using a 32 element microelectrode arrayJournal of Neuroscience Methods, Vol. 23, No. 2Numerical analysis of electrotonus in multicompartmental neuron modelsJournal of Neuroscience Methods, Vol. 19, No. 1Changes in free calcium ion concentration recorded inside hippocampal pyramidal cells in situBrain Research, Vol. 374, No. 1Responses of neurons in isolated preparations of the mammalian central nervous systemProgress in Neurobiology, Vol. 27, No. 4A simple algorithm for solving the cable equation in dendritic trees of arbitrary geometryJournal of Neuroscience Methods, Vol. 12, No. 4Membrane resistivity estimated for the purkinje neuron by means of a passive computer modelNeuroscience, Vol. 14, No. 1In vivo and in vitro studies on putative interneurones in the rat hippocampus: Possible mediators of feed-forward inhibitionBrain Research, Vol. 293, No. 2Cellular bases of hippocampal EEG in the behaving ratBrain Research Reviews, Vol. 6, No. 2Quantitative morphological analysis of spinal motoneuronsBrain Research, Vol. 253, No. 1-2Voltage-clamp analysis of muscarinic excitation in hippocampal neuronsBrain Research, Vol. 250, No. 1Variations in electrophysiological properties of hippocampal neurons in different subfieldsBrain Research, Vol. 242, No. 2Simulation of intrinsic bursting in CA3 hippocampal neuronsNeuroscience, Vol. 7, No. 5The double dipole model of theta rhythm generation: Simulation of laminar field potential profiles in dorsal hippocampus of the ratBrain Research, Vol. 235, No. 1Long-term synaptic enhancement in hippocampus is not regulated by postsynaptic membrane potentialBrain Research, Vol. 233, No. 1Simulation of post-synaptic activities in hippocampal cells during theta rhythmBrain Research Bulletin, Vol. 7, No. 2Modelling the postsynaptic location and magnitude of tonic conductance changes resulting from neurotransmitters or drugsNeuroscience, Vol. 6, No. 5Morphology of physiologically identified neuronsTrends in Neurosciences, Vol. 4 More from this issue > Volume 44Issue 1July 1980Pages 184-99 https://doi.org/10.1152/jn.1980.44.1.184PubMed7420134History Published online 1 July 1980 Published in print 1 July 1980 Metrics

Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.

Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.