Yoram Grossman

• PhD
• Head, Laboratory for Cellular and Molecular Hyperbaric Neurophysiology at Ben-Gurion University of the Negev

Professional divers exposed to pressures greater than 11 ATA (1.1 MPa) may suffer from high-pressure neurological syndrome (HPNS). Divers who use closed-circuit breathing apparatus and patients and medical attendants undergoing hyperbaric oxygen therapy (HBOT) face the risk of CNS hyperbaric oxygen toxicity (HBOTx) at oxygen pressure above 2 ATA (0...

Professional divers exposed to pressures greater than 1.1 MPa may suffer from the high pressure neurological syndrome (HPNS). Divers who use closed-circuit breathing apparatus face the risk of CNS hyperbaric oxygen toxicity (HBOTox). Both syndromes are characterized by reversible CNS hyperexcitability, accompanied by cognitive and motor deficits. P...

Professional divers who are exposed to high pressure (HP) above 1.1 MPa suffer from high pressure neurological syndrome (HPNS), which is characterized by reversible CNS hyperexcitability and cognitive and motor deficits. HPNS remains the final major constraints on deep diving at HP. Prolonged and repetitive exposure to HP during deep sea saturation...

Professional divers exposed to ambient pressures above 11 bar develop the high pressure neurological syndrome (HPNS), manifesting as central nervous system (CNS) hyperexcitability, motor disturbances, sensory impairment, and cognitive deficits. The glutamate-type N-methyl-D-aspartate receptor (NMDAR) has been implicated in the CNS hyperexcitability...

Sequence alignment of GluN1 subunit in different marine and terrestrial mammals.

Sequence alignment of GluN2B subunit in different marine and terrestrial mammals.

Sequence alignment of GluN2A subunit in different marine and terrestrial mammals.

Divers that are exposed to high pressure(HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome(HPNS),which is implicated with central nervous system(CNS) malfunction. Marine mammals performing extended and deep breath-hold dives are exposed to almost 20 MPa without apparent HPNS symptoms. N-methyl-D-aspartate receptor(NMDAR) has repeate...

Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with CNS hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversibl...

Exposure to hyperbaric pressure (HP) exceeding 100 msw (1.1 MPa) is known to cause a constellation of motor and cognitive impairments named high-pressure neurological syndrome (HPNS), considered to be the result of synaptic transmission alteration. Long periods of repetitive HP exposure could be an occupational risk for professional deep-sea divers...

Professional deep-water divers exposed to hyperbaric pressure (HP) above 1.1MPa develop High Pressure Neurological Syndrome (HPNS), which is associated with CNS hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible...

Professional deep sea divers experience motor and cognitive impairment, known as High Pressure Neurological Syndrome (HPNS), when exposed to pressures of 100 msw (1.1 MPa) and above, considered to be the result of synaptic transmission alteration. Previous studies have indicated modulation of presynaptic Ca(2+) currents at high pressure. We directl...

We simulate the inhibition of Ia-glutamatergic excitatory postsynaptic potential (EPSP) by preceding it with glycinergic recurrent (REN) and reciprocal (REC) inhibitory postsynaptic potentials (IPSPs). The inhibition is evaluated in the presence of voltage-dependent conductances of sodium, delayed rectifier potassium, and slow potassium in five -mo...

Professional deep-water divers exposed to high pressure (HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome (HPNS), which is associated with CNS hyperexcitability. We have previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible...

The role of hypercapnia in terminating trigeminal (Vth) nerve inhibition of respiration is not clear. Phrenic nerve responses to Vth nerve stimulation were examined during eucapnia and hypercapnia. We hypothesized that hypercapnic stimulation might not be sufficient to overcome the inhibitory effects of the Vth nerve, and thus would fail to restore...

The high pressure neurological syndrome develops during deep-diving (>1.1 MPa) involving impairment of cognitive functions, alteration of synaptic transmission and increased excitability in cortico-hippocampal areas. The medial perforant path (MPP), connecting entorhinal cortex with the hippocampal formation, displays synaptic frequency-dependent-d...

Known and unpublished data regarding hyperbaric pressure (HP) effects on voltage dependent-Ca2+ channels (VDCCs) were reviewed in an attempt to elucidate their role in the development of high-pressure neurological syndrome (HPNS). Most postulated effects from studies performed in the last two decades (e.g., depressed maximal current) rely on indire...

Human divers exposed to hyperbaric pressure may suffer from cognitive and motor impairments thought to be related to high pressure effects per ce. These effects, termed high pressure neurological syndrome (HPNS), appear at pressure above 1.1 MPa. HPNS involves CNS hyperexcitability that is partially attributed to augmented responses of the glutamat...

Neurodevelopmental disorders, such as schizophrenia and autism, have been associated with disturbances of the GABAergic system in the brain. We examined immediate and long-lasting influences of exposure to the GABA-potentiating drug vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex, before and during the developmental...

We simulate reconstructed α-motoneurons (MNs) under physiological and morphological realistic parameters and compare the modeled reciprocal (REC) and recurrent (REN) inhibitory postsynaptic potentials (IPSPs) containing voltage-dependent channels on the dendrites with the IPSPs of a passive MN model. Three distribution functions of the voltage-depe...

High pressure, which induces central nervous system (CNS) dysfunction (high-pressure neurological syndrome) depresses synaptic transmission at all synapses examined to date. Several lines of evidence indicate an inhibitory effect of pressure on Ca(2+) entry into the presynaptic terminal. In the present work we studied for the first time the effect...

Five reconstructed α-motoneurons (MNs) are simulated under physiological and morphological realistic parameters. We compare the resulting excitatory postsynaptic potential (EPSP) of models, containing voltage-dependent channels on the dendrites, with the EPSP of a passive MN and an active soma and axon model. In our simulations, we apply three diff...

Antiepileptic drugs acting through the potentiation of GABAergic pathways have adverse effects on brain development. Increased risk of impaired intellectual development has been reported in children born to women treated for epilepsy during pregnancy. We have previously shown, in mice, that treatment with the antiepileptic drug vigabatrin (GVG) on...

We simulated a reconstructed α-motoneuron by using realistic physiological and morphological parameters. In our simulations, we examined two distribution functions of the voltage-dependent sodium and potassium channels on the dendrites: (1) exponential decay (ED), illustrated by a high conductance density located proximal to the soma, exponentially...

Pressure above 1.1 MPa induces in mammals and humans the high pressure neurological syndrome (HPNS). HPNS is characterized by cognitive and motor decrements associated with sleep disorders, EEG changes, tremor, and convulsions that ultimately may lead to death. Previous theories proposed that augmented response of the glutamatergic N-methyl-D-aspar...

We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a pha...

In humans, hyperbaric pressure induces the high-pressure neurological syndrome (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic changes, and impairment of cognitive and motor performances. In animals, higher pressures result in convulsions and death. An increased N-methyl-d-aspartate receptor (NMDAR) response has be...

Spliced isoforms of the Na+/Ca2+ exchanger, NCLX, truncated at the alpha-repeat region have been identified. The activity and functional organization of such proteins are, however, poorly understood. In the present work, we have studied Na+/Ca2+ exchange mediated by single alpha-repeat constructs (alpha1 and alpha2) of NCLX. Sodium-dependent calciu...

Exposure to high pressures (HP) has been associated with the development of the high pressure neurological syndrome (HPNS) in deep-divers and experimental animals. In contrast, many diving mammals are naturally able to withstand very high pressures. Although at a certain pressure range humans are also able to perform to some extent, the severe sign...

Learning-associated cellular modifications were previously studied experimentally in the rat piriform cortex after operand conditioning. The results showed a 19% reduction in the level of the action potential after-hyperpolarization (AHP) in trained rats, while the spike trains indicated decreased adaptation during long depolarization. Paradoxicall...

INTRODUCTION In humans, and other terrestrial animals, acoustic and non-acoustic detrimental effects of noise have been described long ago. In recent years there is an increased interest in the damaging consequences of acoustic pollution to marine life. The general increase in underwater noise and the use of sonar are associated with pathological c...

High pressure (>1.0 MPa) induces the high-pressure neurological syndrome (HPNS) characterized by increased excitability of the CNS and cognitive impairments involving memory disorders. The perforant-path transfer of cortical information to the hippocampal formation is important for memory acquisition. High pressure may alter information transfer in...

Modeling of excitation and inhibition of morphologically and physiologically characterized triceps surea motoneuron (MN 42) was executed by a NEURON simulator. The voltage-dependent channels of MN 42 were allocated on six dendrites (the rest six dendrites remained passive) according to three types of distribution functions: a step function (SF), an...

High pressure (>1.5 MPa) induces a series of disturbances of the nervous system that are generically termed high-pressure nervous syndrome (HPNS). HPNS is characterized by motor and cognitive impairments. The neocortex and the hippocampus are presumably involved in this last disorder. The medial perforant path (MPP) synapse onto the granule cells o...

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in p...

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in p...

The effects of low concentrations of 4-aminopyridine (4-AP) on the membrane properties of guinea pig cerebellar Purkinje cells were investigated in slice preparation using intracellular recordings. It was found that 1–10µM 4-AP did not affect the resting potential or the input resistance of the cells, but reduced markedly the duration of the slowly...

Learning-related modifications in predisposition for long-term potentiation (LTP) and long-term depression (LTD) were studied in brain slices of the rat piriform cortex following olfactory learning. Rats were trained to discriminate between pairs of odors until they demonstrated rule learning. We have previously shown that such training is accompan...

Recordings from cerebellar Purkinje cell dendrites have revealed that in response to sustained current injection, the cell firing pattern can move from tonic firing of Ca(2+) spikes to doublet firing and even to quadruplet firing or more complex firing. These firing patterns are not modified substantially if Na(+) currents are blocked. We show that...

Mammalian spinal monosynaptic Ia EPSP and its postsynaptic reciprocal depolarizing inhibition was studied using NEURON simulator in a morphologically and physiologically characterised α-motoneuron. Low gNa and gK located at the dendrites greatly enhanced EPSPA+N maximal amplitude and its reciprocal inhibition. A small area of active dendrite is suf...

We studied the role of acetylcholine (ACh) in creating learning-related long-lasting modifications in the rat cortex. Rats were trained to discriminate positive and negative cues in pairs of odors, until they demonstrated rule learning and entered a mode of high capability for learning of additional odors. We have previously reported that pyramidal...

We studied the effect of olfactory learning on the dendritic spine density of pyramidal neurons in the rat piriform (olfactory) cortex. Rats were trained to distinguish between two pairs of odours in an olfactory discrimination task. Three days after training completion, rats were killed and layer II pyramidal neurons identified by Golgi impregnati...

High pressure induces CNS hyperexcitability while markedly depressing synaptic transmitter release. We studied the effect of pressure (up to 10.1 MPa) on the parallel fibre (PF) synaptic response in biplanar cerebellar slices of adult guinea pigs. Pressure mildly reduced the PF volley amplitude and to a greater extent depressed the excitatory field...

Learning-related cellular modifications were studied in the rat piriform cortex after operand conditioning. Rats were trained to discriminate positive cues in pairs of odors. In one experimental paradigm, rats were trained to memorize 35-50 pairs of odors ("extensive training"). In another paradigm, training was continued only until rats acquired t...

The effects of input distribution in dendrites on postsynaptic inhibition of spinal monosynaptic reflex were studied in morphologically and physiologically characterized α-motoneurons. In homogeneous (HOM) and heterogeneous (HEM) models, the location of the excitatory and inhibitory synapses was randomly selected for each bin of dendritic length. I...

Our purpose was to evaluate in vitro the effect of a high partial pressure of carbon dioxide environment used in laparoscopy on metabolic and immune response of various human peritoneal cells. Polymorphonuclear leukocytes were obtained from 5 healthy volunteers, peritoneal macrophages were obtained from the effluent of 8 patients undergoing continu...

 The effects of high pressure (up to 10.1 MPa) on the spontaneous firing of Purkinje neurons in guinea-pig cerebellar slices were studied using the macropatch clamp technique. Pressure did not significantly alter the single somatic Na+ spike parameters or the frequency of regular Na+ spike firing. When Na+ currents were blocked by 0.5–1 µM tetrodot...

The pattern of sustained Ca2+ spike firing was investigated, using macropatch clamp and intracellular recordings, in guinea pig cerebellar Purkinje cells. Under our standard experimental conditions (30°C, 5 mM [K+]o, 2 mM [Ca2+]o, 1 μM tetrodotoxin), each firing period started with uniform firing and gradually turned into a doublet pattern with a l...

Learning-related cellular modifications were studied in the rat piriform cortex. Water-deprived rats were divided to three groups: 'trained' rats were trained in a four-arm maze to discriminate positive cues in pairs of odours, 'control' rats were 'pseudo-trained' by random water rewarding, and 'naive' rats were water-deprived only. In one experime...

The relation between membrane potential and ciliary beat frequency was examined in tissue cultures from frog palate and esophagus. It was found that hyperpolarization or depolarization of the ciliary cell membrane enhances ciliary beating. The induced enhancement of the ciliary beat frequency by either hyperpolarization or depolarization depends on...

The effects of changes in gamma-aminobutyric acid (GABA) metabolism or inhibitory processes was studied in the perforant path-dentate gyrus synapses in rat cortico-hippocampal slices, and in the monosynaptic-reflex circuit in isolated newborn, rat spinal cord. GABA metabolism was modulated by pharmacological block of either the anabolic enzyme glut...

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of 3-mercaptopropionic acid (MP) and aminooxyacetic acid (AOAA), glutamate decarboxylase (GAD) blockers, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish (Procambarus cla...

The cellular mechanisms underlying the effect of high pressure on synaptic transmission at two types of synapses were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded using a loose macropatch clamp technique at normal pressure and 3.5, 6.9 MPa helium pressure. Responses of the single ex...

The cellular mechanisms underlying the effect of high pressure on synaptic transmission were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded using a loose macropatch-clamp technique at normal pressure and 3.5, 6.9 MPa helium pressure. Responses of the single excitatory axon could be gr...

1. Epileptiform activity was induced in rat neocortical brain slices by application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In intracellular recordings from regular spiking neurons, the activity was characterized by prolonged, all-or-none depolarizing events, with variable delay to a threshold stimulus. 2. At this concentratio...

Cellular membrane potential and ciliary motility were examined in tissues cultures prepared from frog palate and esophagus epithelia. Addition of micromolar concentrations of extracellular ATP caused membrane hyperpolarization and enhanced the beat frequency. These two effects of ATP were 1) dose dependent, reaching a maximum at 10 microM ATP; 2) d...

The cellular mechanisms underlying the effects of high pressure, GABAergic presynaptic inhibition, and low [Ca2+]0 on glutamatergic excitatory synaptic transmission were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded with or without prior stimulation of the inhibitor using a loose mac...

1. Rats were chemically kindled by systemic administration of pentylenetetrazole (PTZ) every 48 h. An initially subthreshold dose that did not elicit a motor response when first applied caused severe epileptiform seizures when the animal was kindled. Once kindled, animals continued to respond to the initially subthreshold dose with a full-blown sei...

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of ethanolamine-O-sulfate (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish opener neuromuscular synapses. 2....

A high-pressure chamber that can be used inside the sample chamber of a spectrofluorometer is described and some performance characteristics are presented. The chamber body, constructed of 316 stainless steel, is temperature regulated using resistive heating elements and a microprocessor-based proportional integral derivative controller. The chambe...

Pressure, like temperature, is one of the fundamental physical variables which constrain living entities. Because it is difficult to manipulate pressure as an experimental variable, however, it has not been a subject of casual study; indeed, very powerful motivation is required to pursue studies of pressure effects. Fortunately, the pressure domain...

High pressure induces hyperexcitability and convulsions in both intact and decerebrated animals. However, pressure suppresses synaptic transmission in isolated invertebrate preparations. We examined the effect of high pressure on monosynaptic (MSR) and polysynaptic (PSR) reflexes in isolated spinal cords of newborn rats. Reflex activity was recorde...

1. The effects of pressure on synaptic currents were examined in crayfish abdominal muscles. 2. Helium pressure (10.1 MPa) considerably decreased extracellularly-recorded excitatory junctional potentials associated with increased short-term facilitation. 3. These effects could be mimicked by a reduction of [Ca2+]o, and partially compensated by an i...

The frequency-dependent effect of various anticonvulsant drugs on the conduction in central axons was studied in the corpus callosum of rat and guinea pig brain slices from the parietal region. Extracellularly recorded compound action potentials (CAPs) were evoked by either single stimulus or high frequency stimulation (40-80 Hz). The CAP in rats c...

Saturation of a liquid with gas before perfusing a tissue or cellular preparation under pressure can be achieved by bubbling the gas through the liquid. A container for this purpose that is housed in the pressure chamber with the preparation allows saturation of the liquid under hyperbaric conditions. Sealing the container allows saturation with a...

We examined the effect of high pressure (10.1 MPa) on the sensitivity of the respiratory center to alterations in pH (range 5.8-7.6) which were obtained by varying either PCO2 or [HCO3-] in superfused Krebs solution. Isolated rat brainstem-spinal cord preparations were placed in a pressure chamber and respiratory-related motor neuron activity was r...

gamma-Aminobutyric acid (GABA) activated channels have a considerable permeability to bicarbonate ions (HCO3-), which might alter the efficacy of chloride-dependent synaptic inhibition. Saturation of the bicarbonate-buffered physiologic solution with 15% CO2/85% O2 increased the depolarizing inhibitory postsynaptic potential (IPSP) amplitude in cra...

Exposure to hyperbaric pressure causes a constellation of motor disturbances and ventilatory difficulties in animals and humans. The present experiments were designed to examine the effects of hyperbaric pressure on the rhythmic activity of the respiratory center in the absence of peripheral sensory afferents by using the isolated brain stem-spinal...

Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-2...

High pressure and anaesthetic agents are mutual antagonists in intact animals, but antagonism is not observed in isolated nerve cells. In order to test the hypothesis that a neural network might display pressure—anaesthetic antagonism not found in simpler systems, we have examined the effects of pentobarbitone at normal pressure and at 10.1 MPa hel...

Guinea pig cerebrocortical synaptosome preparations were used to study the effect of compression to 62 ATA on 45Ca2+ uptake and [3H]GABA release using a calcium ionophore A 23187, which bypasses the voltage-sensitive calcium channel. Pressure was found to exert a suppressive effect on the A 23187-induced release of [3H]GABA, while having no signifi...

The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xanthine oxidase produced a significant depression in evoked release, with no change in either res...

Hyperbaric pressure induces hyperexcitability, tremor, and convulsions in intact animals by mechanisms that are not understood. High pressure induces spontaneous electrical discharges in the spinal ventral roots which we call "tremor-associated activity" (TAA). This study examined the nature of TAA, its likely origins, and its possible contribution...

We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that...

1. Previous studies have shown that hyperbaric pressure depresses synaptic transmission and have suggested that the effect is primarily on transmitter release. The present study analysed the effects of pressure at a crustacean neuromuscular junction. Changes in pressure were compared to changes in extracellular calcium concentration [Ca2+]o with re...

Hyperbaric pressure induces hyperexcitability and convulsions in intact animals by mechanisms that are not understood. In the present experiments we examined the effects of pressure on medullospinal reflexes and synaptic interactions in the vitro brainstem-spinal cord of newborn rats. Reflex activity was recorded extracellularly from the cut ventra...

1. Because hyperbaric pressure profoundly depresses excitatory synaptic transmission, it has proved difficult to account for its excitatory effects in the CNS. We tested the hypothesis that hyperbaric pressure might increase excitation by enhancing facilitation and potentiation during repetitive synaptic activation, and/or by selectively depressing...