Intracellular Recording Of Neurons Research Articles

An exact mathematical description of computation with transient spatiotemporal dynamics in a complex-valued neural network

Networks throughout physics and biology leverage spatiotemporal dynamics for computation. However, the connection between structure and computation remains unclear. Here, we study a complex-valued neural network (cv-NN) with linear interactions and phase-delays. We report the cv-NN displays sophisticated spatiotemporal dynamics, which we then use, in combination with a nonlinear readout, for computation. The cv-NN can instantiate dynamics-based logic gates, encode short-term memories, and mediate secure message passing through a combination of interactions and phase-delays. The computations in this system can be fully described in an exact, closed-form mathematical expression. Finally, using direct intracellular recordings of neurons in slices from neocortex, we demonstrate that computations in the cv-NN are decodable by living biological neurons as the nonlinear readout. These results demonstrate that complex-valued linear systems can perform sophisticated computations, while also being exactly solvable. Taken together, these results open future avenues for design of highly adaptable, bio-hybrid computing systems that can interface seamlessly with other neural networks.

Intracellular neuronal recording in awake nonhuman primates.

Intracellular neuronal recordings from the brain of awake nonhuman primates have remained difficult to obtain because of several formidable technical challenges, such as poor recording stability and difficulties in maintaining long-term recording conditions. We have developed a technique to record neuronal activity by using a coaxial guide tube and sharp electrode assembly, which allows researchers to repeatedly and reliably perform intracellular recordings in the cortex of awake marmosets. Recordings from individual neurons last from several minutes to more than an hour. A key advantage of this approach is that it does not require dura removal, permitting recordings over weeks and months in a single animal. This protocol describes the step-by-step procedures for construction of a custom-made marmoset chair, head-cap implantation, preparation of the sharp electrode and guide tube, neuronal recording and data analysis. As the technique is practical and easy to adapt, we anticipate that it can also be applied to other mammalian models, including larger-size nonhuman primates.

Neuroanatomical and neurophysiological mechanisms of acoustic and weakly electric signaling in synodontid catfish.

To what extent do modifications in the nervous system and peripheral effectors contribute to novel behaviors? Using a combination of morphometric analysis, neuroanatomical tract‐tracing, and intracellular neuronal recording, we address this question in a sound‐producing and a weakly electric species of synodontid catfish, Synodontis grandiops, and Synodontis nigriventris, respectively. The same peripheral mechanism, a bilateral pair of protractor muscles associated with vertebral processes (elastic spring mechanism), is involved in both signaling systems. Although there were dramatic species differences in several morphometric measures, electromyograms provided strong evidence that simultaneous activation of paired protractor muscles accounts for an individual sound and electric discharge pulse. While the general architecture of the neural network and the intrinsic properties of the motoneuron population driving each target was largely similar, differences could contribute to species‐specific patterns in electromyograms and the associated pulse repetition rate of sounds and electric discharges. Together, the results suggest that adaptive changes in both peripheral and central characters underlie the transition from an ancestral sound to a derived electric discharge producing system, and thus the evolution of a novel communication channel among synodontid catfish. Similarities with characters in other sonic and weakly electric teleost fish provide a striking example of convergent evolution in functional adaptations underlying the evolution of the two signaling systems among distantly related taxa.

Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats.

Decerebration permits neurophysiological experimentation absent the confounding effects of anesthesia. Use of the unanesthetized decerebrate preparation in vivo offers several advantages compared with recordings performed in reduced slice preparations, providing the capacity to perform extracellular and intracellular neuronal recordings in the presence of an intact brainstem network. The decerebration procedure typically generates variable degrees of blood loss, which often compromises the hemodynamic stability of the preparation. We describe our microsurgical techniques and discuss microsurgical pearls utilized in order to consistently generate normotensive supracollicularly decerebrate preparations of the rat, exhibiting an augmenting pattern of phrenic nerve discharge. In brief, we perform bilateral ligation of the internal carotid arteries, biparietal craniectomies, securing of the superior sagittal sinus to the overlying strip of bone, removal of the median strip of bone overlying the superior sagittal sinus, supracollicular decerebrative encephalotomy, removal of the cerebral hemispheres, and packing of the anterior and middle cranial fossae with thrombin soaked gelfoam sponges. Hypothermia and potent inhalational anesthesia ensure neuroprotection during postdecerebrative neurogenic shock. Advantages of our approach include a bloodless and fast operation with a nil percent rate of operative mortality. We allow animal arterial pressure to recover gradually in parallel with gentle weaning of anesthesia following decerebration, performed contemporaneously with the provision of the neuromuscular antagonist vecuronium. Anesthetic weaning and institution of vecuronium should be contemporaneous, coordinate, gentle, gradual, and guided by the spontaneous recovery of the arterial blood pressure. We describe our microsurgical techniques and perioperative management strategy designed to achieve decerebration and accordingly survey the literature on techniques used across several studies in achieving these goals.

A Target-Detecting Visual Neuron in the Dragonfly Locks on to Selectively Attended Targets.

The visual world projects a complex and rapidly changing image onto the retina of many animal species. This presents computational challenges for those animals reliant on visual processing to provide an accurate representation of the world. One such challenge is parsing a visual scene for the most salient targets, such as the selection of prey amid a swarm. The ability to selectively prioritize processing of some stimuli over others is known as 'selective attention'. We recently identified a dragonfly visual neuron called 'Centrifugal Small Target Motion Detector 1' (CSTMD1) that exhibits selective attention when presented with multiple, equally salient targets. Here we conducted in vivo, electrophysiological recordings from CSTMD1 in wild-caught male dragonflies (Hemicordulia tau), while presenting visual stimuli on an LCD monitor. To identify the target selected in any given trial, we uniquely modulated the intensity of the moving targets (frequency tagging). We found that the frequency information of the selected target is preserved in the neuronal response, while the distracter is completely ignored. We also show that the competitive system that underlies selection in this neuron can be biased by the presentation of a preceding target on the same trajectory, even when it is of lower contrast than an abrupt, novel distracter. With this improved method for identifying and biasing target selection in CSTMD1, the dragonfly provides an ideal animal model system to probe the neuronal mechanisms underlying selective attention.SIGNIFICANCE STATEMENT We present the first application of frequency tagging to intracellular neuronal recordings, demonstrating that the frequency component of a stimulus is encoded in the spiking response of an individual neuron. Using this technique as an identifier, we demonstrate that CSTMD1 'locks on' to a selected target and encodes the absolute strength of this target, even in the presence of abruptly appearing, high-contrast distracters. The underlying mechanism also permits the selection mechanism to switch between targets mid-trial, even among equivalent targets. Together, these results demonstrate greater complexity in this selective attention system than would be expected in a winner-takes-all network. These results are in contrast to typical findings in the primate and avian brain, but display intriguing resemblance to observations in human psychophysics.

Unexpected plant odor responses in a moth pheromone system.

Male moths rely on olfactory cues to find females for reproduction. Males also use volatile plant compounds (VPCs) to find food sources and might use host-plant odor cues to identify the habitat of calling females. Both the sex pheromone released by conspecific females and VPCs trigger well-described oriented flight behavior toward the odor source. Whereas detection and central processing of pheromones and VPCs have been thought for a long time to be highly separated from each other, recent studies have shown that interactions of both types of odors occur already early at the periphery of the olfactory pathway. Here we show that detection and early processing of VPCs and pheromone can overlap between the two sub-systems. Using complementary approaches, i.e., single-sensillum recording of olfactory receptor neurons, in vivo calcium imaging in the antennal lobe, intracellular recordings of neurons in the macroglomerular complex (MGC) and flight tracking in a wind tunnel, we show that some plant odorants alone, such as heptanal, activate the pheromone-specific pathway in male Agrotis ipsilon at peripheral and central levels. To our knowledge, this is the first report of a plant odorant with no chemical similarity to the molecular structure of the pheromone, acting as a partial agonist of a moth sex pheromone.

State-dependent slow outlasting activities following neocortical kindling in cats

Some forms of electrographic seizures are generated at the level of the cortical network. Neocortical kindling exhibits a resistance to produce generalized convulsive seizures, and therefore, it was rather difficult to use it to study the cortical epileptogenesis. Here, using supra-threshold cortical kindling, we report electrophysiological patterns of field-potential synchronization and intracellular activities in chronically implanted non-anesthetized cats, during different states of vigilance, and during acute seizures elicited by prolonged (20–60 s) electrical stimulation. Acute seizures were easily elicited during transition from slow-wave sleep (SWS) to waking state. The seizures were mainly clonic accompanied with tonic components followed by prolonged postictal depression. Delayed rhythmic outlasting activities (OA) at ~ 1.5 Hz, first time reported here, followed the postictal depression, and lasted up to 2 h. These activities were clear during waking state, slightly reduced during SWS and completely absent during rapid-eye movement sleep. They started focally and following daily stimulations generalized over the entire cortical surface. Extra- and intracellular neuronal recordings during OA displayed spike-doublets, built on the summation of successive excitatory postsynaptic potentials and fast-prepotentials, entailing an increased dendritic excitation. Our results suggest that such rhythmic long-lasting oscillatory activity outlasting seizures are the key factor of epileptogenesis, leading to epilepsy.

Intracellular neuronal recordings form the ventral respiratory group (VRG) and region of the pontine Kölliker‐Fuse nucleus (KF) during vagal entrainment of breathing in rat.

Medullary parts of the respiratory network were associated with respiratory rhythm generation, while pontine parts play a role in secondary modulations of breathing. Recently we identified the KF as key structure that synchronise afferent and network mediated inspiratory off-switch mechanisms (IOS) in response to vagal stimulations (X-stim.). However, potential changes or reconfiguration of the activity patterns of respiratory neurones during synchronisation of IOS are unknown. We performed intracellular recordings to identify changes in neuronal activities during the synchronisation in the perfused brainstem preparation of rats. In the VRG we recorded from 33 respiratory neurones before, during and after repetitive trails of X-stim. Only postinspiratory (PI) and late-I neurones had a clear excitatory response to rhythmic X-stim., while the remaining sub-types of neurones were in summary inhibited. PI and late-I neurones were rhythmically activated by X inputs, but maintained bursting patterns independent of the X-stim. This independent bursting was related to the respiratory rhythm before X-stim. In contrast, recordings of KF neurones (n=12) never showed such stimulus independent bursting. We suggest that the independent bursting of VRG neurones is related to the pontine inputs illustrating the potential interference of the two IOS mechanisms on the cellular level. Funded by BCCN Göttingen

Hyperexcitability of Axotomized and Neighboring Unaxotomized Sensory Neurons Is Reduced Days After Perineural Clonidine at the Site of Injury

Hyperexcitability after peripheral nerve injury occurs in axotomized and neighboring unaxotomized dorsal root ganglion (DRG) neurons and contributes to hypersensitivity. Previous studies have focused on proximal nerve injury and have not examined unaxotomized neurons innervating the site of sensory testing. The current study used a distal nerve injury (partial sciatic nerve ligation [PSNL]), and identified, using fluorescent tracers, axotomized and unaxotomized neurons innervating the site of hypersensitivity. We hypothesized that reduced hypersensitivity after perineural clonidine was associated with reduced hyperexcitability of DRG neurons. Rats underwent sham or PSNL surgery, followed 2 wk later by a single injection at the injury site of clonidine or saline. PSNL, but not sham surgery, reduced hindpaw mechanical withdrawal threshold, and clonidine, but not saline, partially reversed this effect 3 days after injection. Intracellular recording of neurons in whole DRG demonstrated similar changes in membrane properties and excitability in unaxotomized and axotomized neurons after PSNL compared with sham surgery, primarily depolarized resting membrane potential, reduced rheobase, presence of oscillations, and capability to fire repetitively. Most of these changes were present in small-, medium-, and large-diameter neurons. Perineural clonidine 3 days later significantly reversed many of these effects, whereas saline was without effect. We speculate that perineural clonidine reduces signals, likely proinflammatory cytokines and prostaglandins produced during Wallerian degeneration after nerve injury, which drive changes in ion channel expression in DRG somata leading to hyperexcitability and hypersensitivity.

Recruitment of motor neuronal persistent inward currents shapes withdrawal reflexes in the frog

The details of behaviour are determined by the interplay of synaptic connectivity within neuronal circuitry and the intrinsic membrane properties of individual neurones. One particularly dramatic intrinsic property displayed by neurones in many regions of the nervous system is membrane potential bistability, in which transient excitation of a neurone results in a persistent depolarization outlasting the initial excitation. Here we characterize the contribution of such intrinsic bistability, also referred to as plateau properties and mediated by persistent inward currents (PICs), in spinal motor neurones to the production of withdrawal behaviours in the frog. We performed experiments on the isolated frog spinal cord with attached hindlimb. This preparation allowed the simultaneous monitoring of muscle activations during motor behaviour and intracellular neuronal recordings. We found that PICs, following their potentiation by serotonin (5-HT), are recruited and contribute to the production of withdrawal behaviours. These properties conferred a voltage-dependent prolongation to the duration of motor neuronal activity. Consistent with this potentiation of motor neuronal PICs, 5-HT also increased the duration of evoked muscle activations. This behavioural potentiation, as well as the expression of PICs in individual neurones, was reduced following antagonism of L-type Ca(2+) channels. These results demonstrate that PICs in motor neurones can be recruited during the production of behaviour and play a role in specifying the temporal details of motor output.

Effects of lingual nerve afferents on swallowing in sheep.

We investigated in sheep the effects of stimulation of the thick afferent fibers running through the lingual nerve (LN) upon the activity of some of the muscles and medullary interneurons or motoneurons which are active during swallowing. Using electromyography (EMG), and extra- and intracellular neuronal recording, we demonstrated that LN stimulation inhibited triggering and/or distal progression of deglutition reflexly induced by stimulation of the superior laryngeal nerve (SLN). This inhibition appeared as a delay, or the interruption or total suppression, of the EMG and neuronal swallowing activities, depending on the interval between SLN and LN stimulation. It was apparent at the level of the muscles and motoneurons of the nucleus ambiguus, as well as at the level of the interneurons of the dorsal medulla within or around the nucleus of solitary tract, which are assumed to be the core of the organizing system for swallowing, the so-called central pattern generator (CPG). Taking into account the stimulation parameters used in our experiments, it was likely that only LN-mechanosensitive fibers were excited. These fibers were involved in the jaw-opening reflex, and possibly in mastication regulation. Therefore, inhibition of swallowing could result from interactions between the hindbrain mastication and swallowing CPGs. However, it was also possible that mechanosensitive afferents acted upon the swallowing CPG directly or indirectly through supramedullary, especially cortical, loops.

Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus.

Docosahexaenoic acid (DHA) has been suggested to be required for neuronal development and synaptic plasticity. However, in view of the fact that DHA facilitates NMDA responses and blocks K(+) channels, it might predispose the neurons to epileptiform bursting. By using extracellular recording of population spikes in the CA1 region of rat hippocampal slices, we tested this possibility by examining the effect of DHA on the epileptiform activity induced by bicuculline or in Mg(2+)-free medium. When stimuli were delivered to the Schaffer collateral/commissural pathway every 20 or 30 sec, DHA had no significant effect on the epileptiform activity. However, when the frequency of stimulation was increased to 0.2 Hz, DHA attenuated the amplitude of the bursting activity induced by bicuculline to 57.5+/- 10.8% and those induced by Mg(2+)-free ACSF to 65.8+/-13.9% of control. DHA reduced the slope of field excitatory postsynaptic potential (fEPSP) to 77.1+/-7.4% of baseline, without significant effect on the ratio of paired-pulse facilitation (PPF). By intracellular recording of neurons in the stratum pyramidale of rat hippocampal slices, we found that DHA markedly inhibited the repetitive firing of action potentials elicited by depolarizing current pulses but did not affect the initial action potential. Thus, DHA may attenuate epileptic activity mainly through the frequency-dependent blockade of Na(+) channels.

Stimulation of the paraventricular nucleus modulates the activity of gut-sensitive neurons in the vagal complex.

There is good evidence that stimulation of the lateral hypothalamus excites neurons in the dorsal vagal complex (DVC), but the data regarding the role of the paraventricular nucleus (PVN) in vagal function are less clear. The purpose of this study was to clarify the effect of PVN stimulation on the activity of neurons in the DVC. We utilized extracellular and intracellular neuronal recordings with intracellular injections of a neuronal tracer to label individual, physiologically characterized neurons in the DVC of rats anesthetized with pentobarbital sodium. Most (80%) of the gut-sensitive dorsal motor nucleus of the vagus (DMNV) neurons characterized in this study exhibited a change in activity during electrical stimulation of the PVN. Stimulation of the PVN caused an increase in the spontaneous activity of 59% of the PVN-sensitive DMNV neurons, and the PVN was capable of modulating the response of a small subset of DMNV neurons to gastrointestinal stimuli. This study also demonstrated that the PVN was capable of influencing the activity of neurons in the nucleus of the solitary tract (NST). Electrical stimulation of the PVN decreased the basal activity of 66% of the NST cells that we characterized and altered the gastrointestinal response of a very small subset of NST neurons. It is likely that these interactions play a role in the modulation of a number of gut-related homeostatic processes. Increased or decreased activity in the descending pathway from the PVN to the DVC has the potential to alter ascending satiety signals, modulate vago-vagal reflexes and the cephalic phase of feeding, and affect the absorption of nutrients from the gastrointestinal tract.

In vitro electrophysiology of neurons in subnuclei of rat inferior colliculus

We compared membrane and synaptic properties of neurons in the three major subdivisions of inferior colliculus (IC), central nucleus (ICc, N=18), external cortex (ICx, N=38), and dorsal cortex (ICd, N=31) of slices from rat IC, using intracellular neuronal recording. Three types of responses occurred in each IC subdivision in response to depolarizing currents: on-type ( N=20), rapidly-adapting ( N=11), and sustained firing ( N=56), which was most common. The on-type neurons have lower input resistances and shorter time constants, with wider and lower amplitude action potentials (APs) than sustained neurons. A calcium-mediated `hump' was often evoked by depolarizing current pulses in ICd neurons (11 of 28), was infrequent in ICx, but was absent in ICc. ICx and ICc neurons often exhibited spontaneous repetitive spike firing, lower repetitive AP firing thresholds, and faster repetitive spike firing than ICd neurons. Calcium-mediated fast after-hyperpolarizations and spike frequency adaptation were regularly seen in IC. Neurons in ICx and ICd, but not ICc, had synaptic responses to stimulation of the collicular commissure (CoIC). In ICx, large epileptiform depolarizing events were often elicited by strong electrical stimulation of CoIC, which was not normally seen in ICd. These results indicate that ICx neurons exhibit a greater degree of synaptic excitability than neurons in ICc or ICd, which may contribute to the proposed role of ICx in pathological IC hyperexcitability.

Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats.

1. The main purposes of this study are to characterize the intracellular and extracellular responses of cells in superficial layers of entorhinal cortex (EC) in chronically epileptic animals, determine whether their altered physiology is dependent on being connected to hippocampus, and investigate whether there is evidence of augmented excitation and inhibitory interneuron disconnection. 2. Functional connectivity was maintained between the hippocampal area and the EC in vitro in a combined rat hippocampal-parahippocampal slice preparation by slicing with a vibratome at a 30-deg angle to the base of the brain. Three groups of animals were studied: naive animals, animals that had experienced a previous episode of (nonconvulsive) self-sustaining limbic system status epilepticus (SSLSE) induced by electrical stimulation resulting in a chronically epileptic state, and animals in an electrode control group. In chronically epileptic rats and the electrode control group, studies were done on tissue contralateral to the side of electrode implantation. 3. Extracellular and intracellular recordings were made from the superficial layers of EC. Neurons in the superficial layers of the EC were activated by stimulation of the deep layers within the EC or the angular bundle adjacent to the EC, which contains axons from EC neurons. Responses could be elicited by antidromic and synaptic mechanisms by stimulation at either site. In addition, a monosynaptic protocol was used that involved direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of the ionotropic glutamate blockers D(-)-2-amino-5-phosphonovaleric acid (APV) and 6,7-dinitroquinoxaline-2-3-dione (DNQX). 4. Responses were collected over a range of stimulus intensities, from very low to high intensities, to construct input/output function (I/O) curves. Amplitudes and durations were measured at the lowest stimulus intensity that elicited a maximum responses. 5. Extracellular field potential responses from electrode controls did not differ from naives qualitatively with respect to morphology of field potential responses or quantitatively with respect to response duration and amplitude. Field potential responses in tissue from post-SSLSE rats differed markedly in morphology from naive and electrode controls, being more complex, significantly longer in duration, and decreased in amplitude. These epileptiform responses were shortened markedly by blockade of N-methyl-D-aspartate (NMDA) receptors with APV, but this manipulation did not convert responses to a normal morphology. These responses were abolished by blockade of non-NMDA mediated ionotropic glutamate receptors with DNQX. 6. During intracellular recordings of neurons in slices from both control and epileptic animals, neurons were quiescent under resting conditions in the absence of electrical stimulation. 7. Intracellular responses in electrode controls were identical to naive, and together were considered "controls." In control tissue, evoked intracellular responses were similar to those previously described and most commonly consisted of an excitatory postsynaptic potential (EPSP) that was blocked partially by the NMDA-receptor antagonist APV, followed by hyperpolarizing potentials, which were identified electrophysiologically and pharmacologically as gamma-aminobuturic acid-A (GABAA)- and GABAB-receptor-mediated inhibitory postsynaptic potentials (IPSPs). EPSPs were blocked completely by DNQX. 8. In chronically epileptic tissue, evoked intracellular responses differed markedly from responses in control animals, exhibiting all-or-none prolonged paroxysmal depolarizing events with multiple superimposed action potentials in response to a single shock. These depolarizing events were reduced in duration and amplitude, but not abolished, in APV. IPSPs were not seen or markedly reduced at all stimulus intensities. These intracellular responses never resembled control responses. Intracellur responss correlated precisely in morphology and duration with extracellular field potentials. (ABSTRACT TRUNCATED)

Technique for repetitive recording from fetal respiratory neurons.

We developed a new method for repetitive recording of medullary neurons in fetal sheep in situ. The technique involves chronically fixing the fetal head to the flank of the ewe by way of a Teflon plate that has a removable window. This window allows direct access of a recording electrode to the floor of the fourth ventricle of the fetus. In four of six fetuses, repetitive recordings lasting 3-4 h were possible for up to 6 days. By operating on younger fetuses and with care, this time span could be extended. This novel method should be useful in the future for extracellular and intracellular recordings of neurons in the developing fetus without disturbing the fetal state and for the study of putative neurotransmitters during development with iontophoretic techniques.

In vivo Intracellular Recording of Neurons in the Supraoptic Nucleus of the Rat Hypothalamus

Abstract Intracellular recordings were made from cells in the hypothalamic supraoptic nucleus in the urethane-anaesthetized male rat using the ventral surgical approach. Impalements lasted from 5 min to 1 h and recorded cells had an input resistance of 55 to 170 megohms. Spikes of over 50 mV were recorded from 14 cells which could be antidromically activated by stimulation of the neural stalk. The spikes showed a hyperpolarizing afterpotential and the broadening characteristic of rapidly firing magnocellular neurons, which recovered rapidly (<200 ms). When depolarized, the cells showed evidence of a transient potassium current. Recurrent synaptic coupling between the recorded cell and adjacent cells would be expected to alter the hyperpolarizing afterpotential of an antidromic spike as compared with a spontaneous spike; no perceptible difference in the waveforms of the different types of spike could be detected in 11 spontaneously active cells. Application of just subthreshold stimuli to the neural stalk did not evoke depolarizing or hyperpolarizing potentials. Suprathreshold shocks to the neural stalk, when the antidromic spike was prevented by collision, also had no discernible effect on membrane potential. Thus intracellular recordings from magnocellular neurons in vivo revealed electrophysiological properties similar to those seen in vitro. No evidence for synaptic interconnection between magnocellular neurons was found in male rats.

Glial localization of adenylate-cyclase-coupled β-adrenoreceptors in rat forebrain slices

Fluorocitrate (FC), a selective inhibitor of glial cell respiration, was used to estimate the extent to which glial cells contain adenylate cyclase-coupled β-adrenoreceptors in rat brain slices. The drug blocked 75–95% of the elevation of cyclic AMP caused by the β-agonist, isoproterenol, in the 4 forebrain regions sampled (frontal and parietal cortex, caudate nucleus, olfactory tubercle). Intracellular recording of neurons in the treated slices confirmed that they were unaffected by FC. Treatment with the neurotoxin, kainic acid, eliminated all electrophysiological activity but did not affect the cAMP response. The results indicate that glial cells contain the preponderance of adenylate-cyclase-coupled β-adrenoreceptors in slices of the rat forebrain and may constitute an important target of the central noradrenergic system in vivo.

Mechanism of the rapid effect of 17 beta-estradiol on medial amygdala neurons.

The mechanism by which sex steroids rapidly modulate the excitability of neurons was investigated by intracellular recording of neurons in rat medial amygdala brain slices. Brief hyperpolarization and increased potassium conductance were produced by 17 beta-estradiol. This effect persisted after elimination of synaptic input and after suppression of protein synthesis. Thus, 17 beta-estradiol directly changes the ionic conductance of the postsynaptic membrane of medial amygdala neurons. In addition, a greater proportion of the neurons from females than from males responded to 17 beta-estradiol.

Potassium activity and changes in glial and neuronal membrane potentials during initiation and spread of afterdischarge in cerebral cortex of cat

Trains of electrical stimuli of increasing intensity were applied to the surface of the anterior suprasylvian gyrus to produce afterdischarges (AD) that remained localized or spread to a recording site 2 cm posteriorly in the same gyrus. The local afterdischarge was associated with a negative steady potential (SP) shift and increases in [K +] 0 that were maximal at or near the surface and gradually decreased in magnitude at deeper layers of the cortex. During spreading AD, recordings at the stimulus site showed a secondary increase in both the SP shift and [K +] 0 at about 400 to 1400 μm below the cortical surface. As the AD invaded the distant recording site it was associated with a comparable negative SP shift and increase in [K+]o. Neither the appearance of local AD nor its spread to the distant recording site were contingent upon critical elevations of [K +] 0. During secondary increases in [K+]o glial depolarizations were less than would be predicted if the membrane potential were determined solely by changes in the ratio of intra- to extracellular [K +]. Smaller deviations from the Nernst equation also occurred during the repolarizing phase of glial depolarization produced by weaker stimuli that did not produce a secondary increase in [ K +] 0. Only immediately after the stimulus train did the relationship between glial depolarization and [K +] 0 approach the expected slope of a K + electrode. Simultaneous intracellular recording of neurons and [K +] 0 did not show an increase in neuronal firing rate or membrane depolarization to account for the additional increase in [K +] 0 during spreading AD. The possible sources of the secondary increase in [K +] 0 and the significance of the failure of glia to depolarize to levels predicted by the Nernst equation are discussed.