A single compartment model of pacemaking in dissasociated Substantia nigra neurons

Spontaneous oscillations in the mid-brain dopaminergic neurons are an important feature of motor control. The degeneration of these neurons is involved in movement disorders, particularly Parkinson’s Disease. Modelling of this activity is an important part of developing an understanding of the pathogenic process. We develop a mathematical paradigm to describe this activity with a single compartment approach and a CellML version is made publicly available. The model explicitly describes the dynamics of the transmembrane potential with changes in the levels of important cations and is consistent with two major observations in the literature regarding its behaviour in the presence of channel blockers. Stability of the model behaviour is determined from the properties of its Monodromy matrix. We also discuss from the perspective of energy, a pharmacological intervention suggested in the treatment of Parkinson’s Disease.     

Electrical activity of neurons in the cat cortex during cooling

Changes of the activity of cortical neurons were studied in the posterior crucial gyrus and in the middle parts of the suprasylvian and ectosylvian gyri on cooling the brain to 18°C and below. In exact experiments it was noted that cooling the cortex to 18.8–21.8° causes a complete cessation of neuron activity. The kinetics of the change of activity under these conditions follows a definite order: first an increase of the frequency of spike discharges is observed (31–27°), then a decrease of their amplitude (at 25–22°), and finally a complete disappearance of neuron activity (at 21.8–18.8°). Discontinuation of the cooling leads to restoration of the activity of the nerve cells in inverse order: low-amplitude high-frequency discharges manifest (at 23–26°), the amplitude of the spikes increases (at 29–31°) and then the initial activity is restored (at 31–32°). The decrease of neuron activity depends on the rate of temperature drop in the cortex. The faster the cortex is cooled, the lower is the temperature at which the neurons cease to function. And conversely, slow cooling of the cortex causes an inactivation of the spike potentials at a higher temperature.S. M. Kirov Gorki State Medical Institute. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 59–63, January–February, 1970.     

Bursting activity in visual neurons of the cat cortex during pattern detection

The time course of neuronal response to presentation of a static flashing slit at different angles and both light spots and light strips moving in different directions was investigated in the Clare-Bishop area of the cat cortex. It was found that orientational and directional tuning patterns were mainly determined by the bursting constituent of the response and could be measured according to the number of spikes per burst or the actual number of bursts. A closed-loop model for pattern detection is introduced to shed light on bursting activity.V. Kapsuko State University, Vil'nius. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 335–343, May–June, 1987.     

Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain

The major symptoms of Parkinson's disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal dopaminergic terminals. Norepinephrine, serotonin, and melanin pigments are also decreased and cholinergic activity is increased. The cause of PD is unknown. Increased methylation reactions may play a role in the etiology of PD, because it has been observed recently that the CNS administration of S-adenosyl-l-methionine (SAM), the methyl donor, caused tremors, hypokinesia, and rigidity; symptoms that resemble those that occur in PD. Furthermore, many of the biochemical changes seen in PD resemble changes that could occur if SAM-dependent methylation reactions are increased in the brain, and interestingly,l-DOPA, the most effective drug used to treat PD, reacts avidly with SAM. So methylation may be important in PD; an idea that is of particular interest because methylation reactions increase in aging, the symptoms of PD are strikingly similar to the neurological and functional changes seen in advanced aging, and PD is age-related. For methylation to be regarded as important in PD it means that, along with its biochemical reactions and behavioral effects, increased methylation should also cause specific neuronal degeneration. To know this, the effects of an increase in methylation in the brain were studied by injecting SAM into the lateral ventricle of rats. The injection of SAM caused neuronal degeneration, noted by a loss of neurons, gliosis, and increased silver reactive fibers in the SN. The degeneration was accompanied with a decrease in SN tyrosine hydroxylase (TH) immunoreactivity, and degeneration of TH-containing fibers. At the injection site in the lateral ventricle it appears that SAM caused a weakening or dissolution of the intercellular substances; observed as a disruption of the ependymal cell layer and the adjacent caudate tissues. SAM may also cause brain atrophy; evidenced by the dilation of the cerebral ventricle. Most of the SAM-induced anatomical changes that were observed in the rat model are similar to the changes that occur in PD, which further support a role of SAM-dependent increased methylation in PD.     

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.     

Spike activity of mesencephalic neurons during nociceptive stimulation of the alert cat

Rate of reorganizations of neuronal impulse activity in the ventromedial parts of the midbrain of alert rats in conditions of nociceptive and non-nociceptive actions is determined by biological value of used stimuli and closely correlates with spontaneous and evoked changes of the motor activity and oscillations of vegetative parameters. The character of reorganizations of discharge activity (activation, inhibition) significantly differs in cells of various types, singled out on the basis of differences of electrophysiological properties and predominantly localized in different parts of the studied brain areas. The revealed characteristics of the functional properties of the neurones are discussed in connection with supposed differences of their neurotransmitter specificity and their role in providing for different chains of adaptive activity of the organism.     

Localization of cholinergic neurons in the cat lower brain stem

The localization of cholinergic neurons in the cat lower brain stem was determined immunocytochemically with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. ChAT-positive neurons were observed in four major cell groups: cranial nerve motor and special visceromotor neurons: parasympathetic preganglionic visceromotor neurons; neurons located in the ponto-mesencephalic tegmentum including area X (or pedunculopontine tegmental nucleus), nucleus laterodorsalis tegmenti (Ldt) of Castaldi, and peri-locus coeruleus alpha (peri-alpha); and neurons located in nucleus reticularis magnocellularis (Mc) and adjacent nucleus reticularis gigantocellularis (Gc) of the medulla.     

Dendritic action potentials of pyramidal tract neurons in the cat sensorimotor cortex

The intracellular activity of pyramidal tract neurons was studied during electrical stimulation of ventrolateral and ventroposterolateral thalamic nuclei in acute experiments on cats immobilized by myorelaxants. Somatic action potentials were observed and spontaneous spikes were also produced by single and rhythmic stimulation of the thalamic nuclei at the rate of 8–14 Hz, by iontophoretic application of strychnine, and by intracellular depolarizing current pulses. These potentials had a relatively low and variable amplitude of 5–60 mV and are presumed to be dendritic action potentials. It is postulated that these variable potentials arise in the dendrites of pyramidal neurons with multiple zones generating such activity. No interaction was observed where somatic and dendritic action potentials occur simultaneously. The possible functional role of dendritic action potentials is discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 435–443, July–August, 1986.     

Effects of modulation of GABA-and noradrenergic transmission on impulse activity of neurons of the cat motor cortex related to realization of an operant reflex to the action of two signals

On unanesthetized cats trained to perform placing movements to the action of two subsequent signals (warning and imperative stimuli), we examined reflex-related impulse activity (IA) of neurons of the motor cortex (field 4) and simultaneous changes in the “slow” cortical potentials (SCP) in the vertex zone. In almost all cases under study, the shift in the SCP toward negativity was associated with a decrease in the frequency of IA within interstimulus intervals; this corresponded to a period of focusing of the animal’s attention on the expected imperative stimulus. Using a microiontophoretic technique, we tried to elucidate the role of GABA-and adrenergic cerebral systems in the genesis of such inhibitory periods. We conclude that, independently of each other but synchronously, both these systems can be involved in the maintenance of processes of active inhibition in the cerebral cortex under conditions of realization of an operant reflex. Neirofiziologiya/Neurophysiology, Vol. 39, No. 1, pp. 62–68, January–February, 2007.     

Cholinergic regulation of the activity of somatosensory cortex neurons during early postnatal ontogeny of the cat

In 11-14 days kittens, about 20% of neurones in the somatosensory cortical zone react to stimulation of subpallidal region which is a source of cholinergic projections to the cerebral cortex. The effect of subpallidal region stimulation is reproduced in case of microiontophoretic acetylcholine application and blocked by atropine what points to its cholinergic nature. Cholinergic stimulation causes inhibition of the background and evoked activities of the cortical neurones while, as it is known, in adult cats, acetylcholine mainly stimulates a reaction of activation. It is postulated that in kittens at the end of the second week of postnatal development, cholinergic innervation of the cortex significantly differs from the definitive one by its quantitative and functional parameters.     

Corticofugal influences on postsynaptic processes in rubrospinal neurons in the cat brain

Composite and unitary EPSPs of red nucleus neurons evoked by stimulation of the sensomotor and association parietal cortex and nucleus interpositus of the cerebellum were studied in acute experiments on cats anesthetized with pentobarbital. A monosynaptic connection was shown to exist between not only the sensomotor, but also the association cortex, and rubrospinal neurons, in which unitary EPSPs appeared during stimulation of the association cortex after a latent period of 1.5–2.7 msec, with a peak rise time of 1.1–3.1 msec and an amplitude of 0.22–0.65 mV. Analysis of the temporal characteristics of the unitary EPSP suggested that synapses formed by fibers from the association cortex occupy a position nearer the soma than synapses formed by axons of sensomotor cortical cells.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 67–74, January–February, 1984.     

Enflurane depresses activity of the medullary inspiratory neurons in the cat

The effect of enflurane on the firing activity (spikes/sec) of the inspiratory neurons of the dorsal respiratory group (DRG) of the medulla oblongata was studied in decerebrate, paralyzed, mechanically ventilated cats before and after bilateral cervical vagotomy. Inspiratory neuronal activity, phrenic neurogram, arterial blood pressure, tracheal pressure, and end tidal CO2 concentration were recorded. Cells whose firing activity was in phase with that of the phrenic nerve were considered inspiratory neurons. Administration of 1 and 2% enflurane in oxygen produced gradual, significant, and dose-dependent depression of the cell activity with cervical vagi either intact or severed. Recovery of the cell activity occurred after termination of enflurane administration. In cats with intact vagi, 10 min after introduction of 1 and 2% enflurane, the cell activity (mean +/- SE) expressed as percentage of the control was 70 +/- 6% (P less than 0.05) and 48 +/- 5% (P less than 0.01), respectively. Bilateral cervical vagotomy did not affect the degree of cell depression due to enflurane. Hypercarbia induced by inhalation of 5% CO2 increased cell activity, but it did not block enflurane-induced cell depression, although it reduced it. It may be concluded that enflurane depresses the activity of the inspiratory neurons of the DRG. The results also suggest that the respiratory depressant effect of enflurane has a central component and that the DRG region may serve as a site to mediate the enflurane-induced respiratory depression.     

Multicomponent synaptic potentials in rubrospinal neurons of cat brain evoked by corticofugal impulses

The compound nature of EPSP occurring in response to stimulation of the sensorimotor area of the cerebral cortex and the association area of the parietal cortex was shown during acute experiments on cats anesthetized by pentobarbital using an intracellular recording technique. The monosynaptic nature of the two first components of EPSP produced by corticofugal impulses spreading at the average rate of 18.5 and 7.5 msec, respectively, was established. It is postulated that these EPSP components are produced by activating the slow conducting pyramidal and corticorubral neurons. In a portion of rubrospinal neurons the first component of EPSP produced by corticofugal impulses was marked by a fast-rising phase and reflected electrophysiological activation of axosomatic synapses. Findings are discussed with regard to mechanisms reorganizing cortical synaptic inputs to the red nucleus neurons.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 665–672, September–October, 1985.     

Method of live microscopy of the neurons of the cat brain]

Method of microscopic study of living nervous elements of the brain stained with vital dyes in the falling light was developed. Investigation of the morphology of neurons, glial cells and vasculo-nervous relations in the cat's cerebral cortex in living state in situ became possible thanks to the proposed method. Conditions were made to observe the patterns of dynamic changes in these structures under effects of different stimuli.