The sources of extracellular potassium accumulation in the CA1 region of hippocampal slices

doi:10.1016/0006-8993(86)90524-X

Brain Research

Volume 369, Issues 1–2, 26 March 1986, Pages 163-167

https://doi.org/10.1016/0006-8993(86)90524-X Get rights and content

Abstract

To estimate the relative contributions of pre- and postsynaptic elements, and of synaptic and action potential-related currents, to the elevation of interstitial potassium ([K⁺]₀) that occurs during neural activation, we measured [K⁺]₀ and focal electrical potential (V_ec) during ortho- and antidromic stimulation, before and after blocking synaptic transmission, in the CA1 region of hippocampal tissue slices in vitro. Single stimulus pulses could cause Δ[K⁺]₀ as large as 0.25 mM in stratum (st.) pyramidale and 0.27 mM in st. radiatum; stimulus trains could cause Δ[K⁺]₀ as large as 10.5 mM in st. pyramidale and 6.25 mM in st. radiatum. Stimulus trains also caused negative V_ec shifts; these shifts were related in a linear fashion to Δ[K⁺]₀. For a given increase in [K⁺]₀, the change in V_ec was greater in st. radiatum than in st. pyramidale. In st. pyramidale, the Δ[K⁺]₀ evoked by antidromic stimulation was 65% of the Δ[K⁺]₀ evoked by orthodromic stimulation (with equal population spike amplitudes). Blockade of synaptic transmission by removal of Ca²⁺ reduced orthodromically evoked Δ[K⁺]₀ in st. radiatum by 52%; Δ[K⁺]₀ in st. pyramidale was abolished. Removal of Ca²⁺ caused an 11% decrease in the Δ[K⁺]₀ evoked in st. pyramidale by antidromic stimulation. We conclude that in the layer of dendritic trees (st. radiatum), approximately half of the K⁺ ions released into the interstitial space during orthodromic stimulation come from presynaptic terminals, with the remainder probably resulting from the ion currents of postsynaptic potentials. Among the pyramidal cell bodies (st. pyramidale), almost all of the excess K⁺ is released by action potential currents.

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Cited by (19)

Interstitial ions: A key regulator of state-dependent neural activity?
2020, Progress in Neurobiology
Citation Excerpt :
In other words, brain function and ion gradients are inseparable. A vast historical literature documents that the concentrations of certain cation species (potassium: K+, calcium: Ca2+ and magnesium: Mg2+) in the interstitial environment dynamically relate to neuronal excitability and activity (Aitken and Somjen, 1986; Baylor and Nicholls, 1969; Dingledine and Somjen, 1981; Heinemann et al., 1990, 1986, 1977; Heinemann and Lux, 1977; Karwoski et al., 1985; Kraig and Nicholson, 1978; Krnjević et al., 1982; Nicholson et al., 1978; Poolos et al., 1987; Poolos and Kocsis, 1990; Singer et al., 1976; Somjen, 1980; Utzschneider et al., 1992; Zanotto and Heinemann, 1983). Still, changes in the milieu of interstitial ions are not traditionally considered to be an integral part of neuronal signaling, circuit activity and global brain states, but rather a byproduct of neuronal activity.
Throughout the nervous system, ion gradients drive fundamental processes. Yet, the roles of interstitial ions in brain functioning is largely forgotten. Emerging literature is now revitalizing this area of neuroscience by showing that interstitial cations (K⁺, Ca²⁺ and Mg²⁺) are not static quantities but change dynamically across states such as sleep and locomotion. In turn, these state-dependent changes are capable of sculpting neuronal activity; for example, changing the local interstitial ion composition in the cortex is sufficient for modulating the prevalence of slow-frequency neuronal oscillations, or potentiating the gain of visually evoked responses. Disturbances in interstitial ionic homeostasis may also play a central role in the pathogenesis of central nervous system diseases. For example, impairments in K⁺ buffering occur in a number of neurodegenerative diseases, and abnormalities in neuronal activity in disease models disappear when interstitial K⁺ is normalized. Here we provide an overview of the roles of interstitial ions in physiology and pathology. We propose the brain uses interstitial ion signaling as a global mechanism to coordinate its complex activity patterns, and ion homeostasis failure contributes to central nervous system diseases affecting cognitive functions and behavior.
Activity-dependent changes of tissue resistivity in the CA1 region in vivo are layer-specific: Modulation of evoked potentials
2001, Neuroscience
We have investigated the spatial map of tissue resistivity across CA1 layers in vivo, its modifications during repetitive orthodromic activity, and the influence of this factor on the shaping of population spikes. Measurement of tissue resistance was made by a high-spatial-resolution three-electrode method. A computer network of equivalent resistors aided theoretical analysis. Tissue resistivity was homogeneous within the basal and apical dendritic trees (260±4.5 and 287±2.6 Ωcm, respectively). In the stratum pyramidale we found a sharply delimited high-resistivity (643±35 Ωcm) band ∼20 μm wide. Resistivity in slices was ∼30% higher than in vivo. Computer analysis indicated that the high-resistance somatic layer has a strong influence on the somatic and proximal dendritic contribution to the shaping of population spikes, and reduces volume propagation of currents between dendritic trees. Repetitive orthodromic activation at the theta frequency (4–5 Hz, 20–30 s) caused a stereotyped cycle of field potentials and layer-specific changes of resistivity. Initially (∼10 s), long-lasting field excitatory postsynaptic potentials and multiple somatodendritic population spikes developed, and resistivity gradually increased in all layers at a similar rate (period average: 11%). Subsequently, the long-lasting field excitatory synaptic potential subsided and dendritic spike generators were strongly reduced, but multiple somatic spikes remained. Concurrently, the resistivity reached a plateau in all dendritic layers but continued to increase in the somatic layer for about 10–15 s (20% average and up to 50% maximum). Recovery required ∼60 s. The orthodromic somatic population spike increased variably during stimulation (up to 60%). Using local resistivity changes for correction, supernormal increments of the population spikes were offset, but not totally, uncovering several sub- and supernormal phases that were partially related to changes in dendritic population spike. These resistivity-independent modulations of the somatic population spike are caused by variable volume spread from dendritic spike currents and changed somatic contribution of firing units.
This report demonstrates that the strong heterogeneity in the stratum pyramidale is an important factor shaping and modulating the population spike. The different regional rates of resistivity variation force the independent correction of local evoked potentials. We show that not doing so may cause bulk errors in the interpretation of, for instance, field potential ratios widely used to measure the population excitability. The present results underscore the importance of checking variations in recording conditions, which are inherent in most experimental protocols.
Synaptic activation of glutamate transporters in hippocampal astrocytes
1997, Neuron
Glutamate transporters in the CNS are expressed in neurons and glia and mediate high affinity, electrogenic uptake of extracellular glutamate. Although glia have the highest capacity for glutamate uptake, the amount of glutamate that reaches glial membranes following release and the rate that glial transporters bind and sequester transmitter is not known. We find that stimulation of Schaffer collateral/commissural fibers in hippocampal slices evokes glutamate transporter currents in CA1 astrocytes that activate rapidly, indicating that a significant amount of transmitter escapes the synaptic cleft shortly after release. Transporter currents in outside-out patches from astrocytes have faster kinetics than synaptically elicited currents, suggesting that the glutamate concentration attained at astrocytic membranes is lower but remains elevated for longer than in the synaptic cleft.
Osmotic effects upon the theta rhythm, a natural brain oscillation in the hippocampal slice
1993, Experimental Neurology
Raising plasma osmolality reduces patient susceptibility to generalized tonic-clonic seizure. In brain slices, elevated osmolality reduces epileptiform discharge. Conversely, lowering osmolality can induce generalized tonic-clonic seizure in patients and promotes epileptiform activity in hippocampal or neocortical slices. Rhythmic slow activity or "theta" encodes memory in some mammals and represents n nonpathological oscillation of cortical neurons. In hippocampal slices, theta consists of a 4-10 Hz oscillation overriding a slow depolarization (SD) that recurs periodically. We examined if the theta rhythm, which is a natural brain oscillation, was affected by clinically relevant changes in osmolality. Theta was induced by bath application of 40 μM carbachol and intracellularly recorded in individual CA3 neurons of the rat hippocampal slice. Artificial CSF (ACSF) elevated by 40 milliosmoles (+40 mOsm) using mannitol slowed the SD frequency in 18 of 18 CA3 neurons. Conversely -40 mOsm ACSF increased SD frequency in 12 of 14 neurons. Osmotic alteration did not change theta frequency in 9 of 9 CA3 cells, but overriding action potentials were reduced in number or eliminated by hyperosmotic ACSF in 8 of 12 neurons. Elevation of osmolality with glycerol, which does not alter cell volume, had no effect in 4 of 4 neurons. This indicated that the induced changes in excitability resulted from alterations in cell volume. We examined if osmotically induced changes in cell volume might alter the glial capacity to buffer K⁺ released by neuronal discharge. Intracellular recordings from glial cells revealed that osmolality had no significant effect upon the glial resting potential itself. In 40 μM carbachol the glial membrane potential slowly oscillated, the depolarizing phase reflecting K⁺ release by discharging neurons during each SD. Elevating or lowering [K⁺]_o had little effect on SD frequency, indicating that osmotic effects did not act through changes in [K⁺]_o which should result from alterations in the extracellular volume. We conclude that neuronal excitability is osmoresponsive, probably through altered synaptic and field effects. However, the theta rhythm itself is not osmoresponsive.
Potassium-induced long-term potentiation in rat hippocampal slices
1992, Brain Research
We observed that a transient increase in extracellular potassium concentration (50 mM for 40 s) was sufficient to induce long-term potentiation (LTP) of synaptic transmission in area CA1 of the hippocampal slice. Potassium-induced potentiation of the Schaffer collateral/commissural synapses demonstrated several features characteristic of tetanus-induced LTP: (1) population excitatory post-synaptic potential (EPSP) amplitudes were enhanced to a similar magnitude (on average 70% above baseline) which (2) lasted for more than 20 min; (3) induction was blocked by bath application of the specific N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphonovalerate (d-APV), and (4) was attenuated by reduction of the concentration of calcium in the extracellular medium. Induction of either potassium-induced LTP or tetanus-induced LTP occluded the subsequent expression of the other. Finally, exposure to high potassium in the absence of electrical stimulation was sufficient to induce LTP. Taken together, these data indicate that brief depolarizing stimuli other than tetanus can induce LTP. Because potassium-induced LTP is not restricted to the subset of afferents examined electrophysiologically, such a method could facilitate analyses of the biochemical events underlying both the induction and expression of LTP.
Septohippocampal disinhibition
1988, Brain Research
Intracellular recordings from CA₁ and $CA_{23}$ neurons in rats under urethane anesthesia revealed the following effects of medial septal stimulation (10 pulse trains at ∼100 Hz): (1) in most cases only minimal signs of any synaptic potential; (2) a marked and prolonged (200–500 ms) depression of on-going inhibitory postsynaptic potentials (IPSPs), particularly evident when IPSPs were reversed by Cl^∗t- injection; (3) a corresponding increase in input resistance: (4) depolarization when recording with non-Cl⁻ containing electrodes; (5) a predominant hyperpolarization when recording with Cl⁻-containing electrodes; and (6) a marked reduction of the variability of resistance and voltage data. These observations indicate that septal stimulation can strongly depress tonic inhibition in the hippocampus. Septal trains also tended to weaken IPSPs evoked in pyramidal cells by fimbrial stimulation, reducing conductance increase during IPSPs by an average of 42% (S.D.±24.3). Septal inputs to the hippocampal CA₁ and $CA_{23}$ regions appear to have a major disinhibitory function.

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The sources of extracellular potassium accumulation in the CA1 region of hippocampal slices

Abstract

Brain Research

Brain Research

Brain Research

Prog. Biophys. Mol. Biol.

Neurosci. Lett.

Paroxysmal discharges and spreading depression in hippocampal slices

Soc. Neurosci. Abstr.

Epileptiform burst after-hyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells

Science

Recurrent inhibition in the hippocampus with identification of the inhibitory cell and its synapses

Nature (London)

Pathway of postsynaptic inhibition in the hippocampus

J. Neurophysiol.

Participation of inhibitory and excitatory interneurons in the control of hippocampal cortical output

Extracellular potassium and calcium changes in hippocampal slices

Brain Research

Physiology of the Cerebrospinal Fluid

The hippocampus

Physiol. Rev.