Presynaptic modulation of Lymnaea neurons evoked by computer-generated spike trains

To investigate the functional organisation and information processing in Lymnaea neuronal networks, artificial spike trains were elicited in one of the main respiratory interneurons (RPeD1) and the modulation of the firing patterns of postsynaptic cells was examined. This was performed by precisely timing the action potential generation of the presynaptic cell using a computer-controlled voltage clamp amplifier (pattern clamp technique). Induced oscillation (0.1-0.4 Hz) in the firing pattern of RPeD1 spread to a large number of postsynaptic cells, as clearly demonstrated by Fourier power spectra. At the same time, no signs of precise (millisecond) spike timing was observed in the cells studied. The results confirm that the neurons used in our experiments process information as pure rate-coders.     

The structure and precision of retinal spike trains

Assessing the reliability of neuronal spike trains is fundamental to an understanding of the neural code. We measured the reproducibility of retinal responses to repeated visual stimuli. In both tiger salamander and rabbit, the retinal ganglion cells responded to random flicker with discrete, brief periods of firing. For any given cell, these firing events covered only a small fraction of the total stimulus time, often less than 5%. Firing events were very reproducible from trial to trial: the timing jitter of individual spikes was as low as 1 msec, and the standard deviation in spike count was often less than 0.5 spikes. Comparing the precision of spike timing to that of the spike count showed that the timing of a firing event conveyed several times more visual information than its spike count. This sparseness and precision were general characteristics of ganglion cell responses, maintained over the broad ensemble of stimulus waveforms produced by random flicker, and over a range of contrasts. Thus, the responses of retinal ganglion cells are not properly described by a firing probability that varies continuously with the stimulus. Instead, these neurons elicit discrete firing events that may be the fundamental coding symbols in retinal spike trains.     

Effects of electrical stimulation of the amygdaloid central nucleus on neocortical arousal in the rabbit

This study sought to determine whether electrical stimulation of the amygdaloid central nucleus (ACe) produces cholinergically mediated neocortical arousal manifested in the suppression of frontal cortex delta wave (1-4 Hz) activity. Stimulation in both anesthetized and conscious rabbits produced a suppression of delta activity that was accompanied by bradycardia and blocked by cholinergic antagonists. Stimulation of the adjacent putamen did not produce delta suppression, whereas stimulation of the adjacent ventral globus pallidus produced a suppression of shorter duration than that produced by ACe stimulation. The results suggest that the ACe influences neocortical arousal, which may be mediated by its influence on the activity of cholinergic neurons of the nucleus basalis.     

Prolactin immunoreactive neurons of the rat lateral hypothalamus: immunocytochemical and ultrastructural studies

A population of neurons immunoreactive to an antiserum (AS) raised against ovine prolactin (LHPLI neurons) was previously described in the rat perifornical areas and lateral hypothalamus. In the present paper, we demonstrate by complementary immunocytochemical studies using AS to various biologically active peptides or neurotransmitters that these neurons are also detected by AS to bradykinin and to dynorphin B. Electron microscope examination shows that the LHPLI neurons are peptidergic neurons synthesizing apparently only one type of secretory granules. Numerous synapses on their perikarya and processes reflect the complexity of their relationships with other neuron populations, which have yet to be mapped and elucidated.     

The contralateral effect of antidromic stimulation of the trigeminal nerve on the rabbit eye

The effect on contralateral eyes after injuries to one eye has been called the consensual reaction and has been postulated to be either the consequence of a neural reflex or one achieved by circulating substances. Trigeminal stimulation always causes ipsilateral miosis, ocular hyperemia, intraocular hypertension, and a disruption of the blood-aqueous barrier. Disruption of the blood-aqueous barrier in the contralateral eye after stimulation of the trigeminal nerve always occurs and depends on intact sensory innervation to that globe in rabbits. The disruption is not prevneted by pretreatment of the animals with indomethacin. The phenomenon of disruption of the barrier is sometimes accompanied by an elevation of intraocular pressure in the contralateral eye but not by the other irritative responses. Thus, unilateral stimulation of a sensory nerve, the trigeminal, in the rabbit, can produce ipsilateral contralateral disruption of the blood-aqueous barrier.     

The voltage-dependent conductances of rat neocortical layer I neurons

Whole cell patch-clamp techniques were used to study voltage-dependent sodium (Na+), calcium (Ca2+), and potassium (K+) conductances in acutely isolated neurons from cortical layer I of adult rats. Layer I cells were identified by means of gamma-aminobutyric acid (GABA) immunocytochemistry. Positive stainings for the Ca2+-binding protein calretinin in a subset of cells, indicated the presence of Cajal-Retzius (C-R) cells. All investigated cells displayed a rather homogeneous profile of voltage-dependent membrane currents. A fast Na+ current activated at about -45 mV, was half-maximal steady-state inactivated at -66.6 mV, and recovery from inactivation followed a two-exponential process (tau1 = 8.4 ms and tau2 = 858.8 ms). Na+ currents declined rapidly with two voltage-dependent time constants, reaching baseline current after some tens of milliseconds. In a subset of cells (< 50%) a constant current level of < 65 pA remained at the end of a 90 ms step. A transient outward current (Ifast) activated approximately -40 mV, declined rapidly with a voltage-insensitive time constant (tau approximately 350 ms) and was relatively insensitive to tetraethylammonium (TEA, 20 mM). Ifast was separated into two components based on their sensitivity to 4-aminopyridine (4-AP): one was blocked by low concentrations (40 microM) and a second by high concentrations (6 mM). After elimination of Ifast by a conditioning prepulse (50 ms to -50 mV), a slow K+ current (I(KV)) could be studied in isolation. I(KV) was only moderately affected by 4-AP (6 mM), while TEA (20 mM) blocked most (> 80%) of the current. I(KV) activated at about -40 mV, declined monoexponentially in a voltage-dependent manner (tau approximately 850 ms at -30 mV), and revealed an incomplete steady-state inactivation. In addition to Ifast and I(KV), indications of a Ca2+-dependent outward current component were found. When Na+ currents, Ifast, and I(KV) were blocked by tetrodotoxin (TTX, 1 microM), 4-AP (6 mM) and TEA (20 mM) an inward current carried by Ca2+ was found. Ca2+ currents activated at depolarized potentials at about -30 mV, were completely blocked by 50 microM cadmium (Cd2+), were sensitive to verapamil (approximately 40% block by 10 microM), and were not affected by nickel (50 microM). During current clamp recordings, isolated layer I neurons displayed fast spiking behaviour with short action potentials (approximately 2 ms, measured at half maximal amplitude) of relative small amplitude (approximately 83 mV, measured from the action potential threshold).     

The time distribution of the spike train activity of the neurons in the rabbit sensorimotor cortex during a rhythmic motor dominant]

A stationary excitation focus produced in rabbit cortex by rhythmical electrodermal paw stimulation was revealed by presentation of testing sound stimuli, which were earlier indifferent for an animal. The multiunit activity in the sensorimotor cortex was recorded. The neuronal pairs were detected with correlated discharges. Analysis of discharges in such pairs revealed the dominant incidence of conjugated impulses with the interval equal or close to 2 s, if the focus had been created by stimulation with the rhythmic interval 2 s. The dominant interval between discharges in a conjugated pair of neurons was equal of close to 3 s, if the rhythmic stimuli positions had been spaced 3 s. It was shown that the rhythmical nature of the dominant focus was maintained at the level of neuronal interactions, i.e., was of a systemic character. The acquired rhythm in conjugated cell activity was observed not only during summation in the moment of excitation transmission to the effector (i.e., when the dominant realized itself in the motor reaction), but within the periods between the testing stimuli.     

The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability

Although signaling between neurons is central to the functioning of the brain, we still do not understand how the code used in signaling depends on the properties of synaptic transmission. Theoretical analysis combined with patch clamp recordings from pairs of neocortical pyramidal neurons revealed that the rate of synaptic depression, which depends on the probability of neurotransmitter release, dictates the extent to which firing rate and temporal coherence of action potentials within a presynaptic population are signaled to the postsynaptic neuron. The postsynaptic response primarily reflects rates of firing when depression is slow and temporal coherence when depression is fast. A wide range of rates of synaptic depression between different pairs of pyramidal neurons was found, suggesting that the relative contribution of rate and temporal signals varies along a continuum. We conclude that by setting the rate of synaptic depression, release probability is an important factor in determining the neural code.     

Cholinergic excitation of dendrites in neocortical neurons

Discharge patterns were studied in response to iontophoretic application of acetylcholine to the soma and dendrites of 128 neocortical pyramidal neurons of layer V. Extracellular recordings were obtained from slices of the guinea-pig parietal cortex. All responses found were excitatory and were better expressed in spontaneously firing cells than in silent ones. Sensitivity to acetylcholine was approximately the same at somatic and dendritic sites in all the cells. Activation of muscarinic receptors gave rise to firing patterns with equal latencies and intensities when applied to both soma and dendrites. The latter suggests that membrane excitation elicited in dendrites by binding of acetylcholine to muscarinic cholinoreceptors is likely to propagate towards the soma through intracellular biochemical processes. Modulating effect of acetylcholine on output firing patterns, elicited by dendritic application of excitatory amino acids, included shortening of the somatic response latency and increase of response intensity and duration. We propose that, in contrast to glutamatergic excitation, the spread of cholinergic excitation along dendrites involves intra-cellular chemical signalling and results in changing the electrical properties of dendrites all over their length.     

The functional organization of the posterior lateral nucleus of the rat hypothalamus

It has been demonstrated that the posterior lateral thalamic nucleus of the rat receives information from the visual, somatic and auditory systems. Some of the neurons (63%) have a convergent input from these systems, although these neurons exhibit functional specificity with respect to the predominant inhibitory influence of the background activity of one of the sensory systems investigated. The other part of the neurons (37%) receives information only from the visual or somatic system, these neurons exhibiting excitatory phasic reaction to sensory stimuli.     

Hippocampal activity, behavior, self-stimulation, and heart rate during electrical stimulation of the lateral hypothalamus.

Observed hippocampal electrical activity in relation to behavior elicited by stimulation of the lateral hypothalamus in 30 male hooded rats. Rhythmical slow activity (RSA) was always present during walking, rearing, digging, bar pressing, and other presumably "voluntary" movements, but at low stimulation intensities it was often absent during licking, chewing, face washing, and other presumably "automatic" movements. At higher stimulation intensities, Ss became hyperactive and RSA was almost continually present. No relation was found between RSA and heart rate or licking movements. An ascending hypothalamic system may require hippocampal participation in the control of voluntary movements, but hippocampal participation may not be required for the control of more automatic movements. (30 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The functional asymmetry of the rabbit medial hypothalamus during the avoidance reaction

We have investigated whether hypoxia and muscle contractions stimulate glucose transport in perfused rat muscle to the same extent, additively and with the same sensitivity to the microbial products calphostin C and wortmannin. Hindlimb glucose uptake increased gradually from 3.4+/-0.5 to a maximal level of 12.7+/-0.6 micromol g-1 h-1 (n=11) after 50 min of hypoxia. Compared with hypoxia, the effect of maximal electrical stimulation of the sciatic nerve on muscle glucose uptake was more than two-fold higher (27+/-2 micromol g-1 h-1 (n=14)). This was due to a higher contraction- vs. hypoxia-induced glucose transport rate in oxidative fibers. The stimulatory effect of hypoxia and electrical stimulation was not additive. Contraction-induced muscle glucose transport was inhibitable by both calphostin C and wortmannin in the micromolar range, whereas the effect of hypoxia was totally insensitive to these drugs. Our data suggest that diacylglycerol/phorbol ester-sensitive protein kinase C is involved in stimulation of muscle glucose transport by contractions and that in contrast to the prevailing concept, hypoxia and contractions do not stimulate muscle glucose transport by the same signaling mechanism.     

Interferon modulates glucose-sensitive neurons in the hypothalamus

Interferon-alpha (IFN) therapy induces feeding suppression that resembles anorexia. The hypothalamic glucose-sensitive neurons engage in feeding behavior. Coronal sections of rat brains, containing both the lateral hypothalamus (LH) and the ventromedial hypothalamus (VMH), as well as single-cell recordings were used to study the interaction between IFN and glucose-sensitive neurons. IFN suppressed the majority (78%) of LH neurons, while reduction in glucose concentration elicited excitation in the majority (85%) of the same neurons. The opposite effects were observed in the VMH, where IFN excited the majority of neurons (61%), and reduction in glucose concentration exerted the opposite effects in 64% of VMH recordings. Concomitant IFN and glucose reduction exhibited only the effects elicited by IFN, regardless of whether the glucose reduction caused excitation (LH) or suppression (VMH). This observation suggests that IFN causes anorexia by modulating the LH and VMH glucose-sensitive neurons.     

Differential signaling via the same axon of neocortical pyramidal neurons

The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto the same morphological class differed in the numbers and dendritic locations of synaptic contacts, their absolute synaptic strengths, as well as their rates of synaptic depression and recovery from depression. The same axon of a pyramidal neuron innervating another pyramidal neuron and an interneuron mediated frequency-dependent depression and facilitation, respectively, during high frequency discharges of presynaptic action potentials, suggesting that the different natures of the target neurons underlie qualitative differences in synaptic properties. Facilitating-type synaptic connections established by three pyramidal neurons of the same class onto a single interneuron, were all qualitatively similar with a combination of facilitation and depression mechanisms. The time courses of facilitation and depression, however, differed for these convergent connections, suggesting that different pre-postsynaptic interactions underlie quantitative differences in synaptic properties. Mathematical analysis of the transfer functions of frequency-dependent synapses revealed supra-linear, linear, and sub-linear signaling regimes in which mixtures of presynaptic rates, integrals of rates, and derivatives of rates are transferred to targets depending on the precise values of the synaptic parameters and the history of presynaptic action potential activity. Heterogeneity of synaptic transfer functions therefore allows multiple synaptic representations of the same presynaptic action potential train and suggests that these synaptic representations are regulated in a complex manner. It is therefore proposed that differential signaling is a key mechanism in neocortical information processing, which can be regulated by selective synaptic modifications.     

Mechanisms underlying the chronotropic effect of angiotensin II on cultured neurons from rat hypothalamus and brain stem

The chronotropic effect of angiotensin II (Ang II) was studied in cultured neurons from rat hypothalamus and brain stem with the use of the patch-clamp technique. Ang II (100 nM) increased the neuronal spontaneous firing rate from 0.8 +/- 0.3 (SE) Hz in control to 1.3 +/- 0.4 Hz (n = 7, P < 0.05). The amplitude of threshold stimulation was decreased by Ang II (100 nM) from 82 +/- 4 pA to 62 +/- 5 pA (n = 4, P < 0.05). These actions of Ang II were reversed by the angiotensin type 1 (AT1) receptor antagonist losartan (1 microM). In the presence of tetrodotoxin, Ang II (100 nM) significantly increased the frequency and the amplitude of the Cd2+-sensitive subthreshold activity of the cultured neurons. Ang II also stimulated the subthreshold early afterdepolarizations (EADs) to become fully developed action potentials. Similar to the action of Ang II, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 100 nM) increased the firing rate from 0.76 +/- 0.3 Hz to 2.3 +/- 0.5 Hz (n = 6, P < 0.05) and increased the neuronal subthreshold activity. After neurons were intracellularly dialyzed with PKC inhibitory peptide (PKCIP, 5 microM), PMA alone, Ang II alone, or PMA plus Ang II no longer increased the action potential firing initiated from the resting membrane potential level. However, superfusion of PMA plus Ang II or Ang II alone increased the number of EADs that reached threshold and produced action potentials even in the presence of PKCIP (5 microM, n = 4). The actions of Ang II could also be mimicked by depolarizing pulse and K+ channel blockers (tetraethylammonium chloride or 4-aminopyridine). These results indicate that Ang II by activation of AT1 receptors increases neuronal excitability and firing frequency, and that this may involve both PKC dependent and -independent mechanisms.     

Projections of GABAergic and cholinergic basal forebrain and GABAergic preoptic-anterior hypothalamic neurons to the posterior lateral hypothalamus of the rat

Within the basal forebrain, gamma-aminobutyric acid (GABA)-synthesizing neurons are codistributed with acetylcholine-synthesizing neurons (Gritti et al. [1993] J. Comp. Neurol. 329:438-457), which constitute one of the major forebrain sources of subcortical afferents to the cerebral cortex. In the present study, descending projections of the GABAergic and cholinergic neurons were investigated to the lateral posterior hypothalamus (LHp) through which the medial forebrain bundle passes and where another major forebrain source of subcortical afferents is situated. Retrograde transport of cholera toxin b subunit (CT) from the LHp was combined with immunohistochemical staining for glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT) using a sequential peroxidase-antiperoxidase (PAP) technique. A relatively large number of GAD+ neurons (estimated at approximately 6,200), which represented > 15% of the total population of GAD+ cells in the basal forebrain (estimated at approximately 39,000), were retrogradely labeled from the LHp. These cells were distributed through the basal forebrain cell groups, where ChAT+ cells are also located, including the medial septum and diagonal band nuclei, the magnocellular preoptic nucleus, and the substantia innominata, with few cells in the globus pallidus. In these same nuclei, a small number of ChAT+ cells were retrogradely labeled (estimated at approximately 800), which represented only a small percentage (< 5%) of the ChAT+ cell population in the basal forebrain (estimated at approximately 18,000). Both the GAD+ and ChAT+ LHp-projecting neurons represented a small subset of their respective populations in the basal forebrain, distinct from the magnocellular, presumed cortically projecting, basal neurons. In addition to the GAD+ cells in the basal forebrain, GAD+ cells in the adjacent preoptic and anterior hypothalamic regions were also retrogradely labeled in significant numbers (estimated at approximately 5,500) and proportion (> 20%) of the total population (estimated at approximately 30,000) from the LHp. The retrogradely labeled GAD+ neurons were distributed in continuity with those in the basal forebrain through the lateral preoptic area, medial preoptic area, bed nucleus of the stria terminals, and anterior and dorsal hypothalamic areas. Of the large number of cells that project to the LHp in the basal forebrain and preoptic-anterior hypothalamic regions (estimated at approximately 66,000), the GAD+ neurons represented a significant proportion (> 15%) and the ChAT+ neurons a very small proportion (approximately 2%). The relative magnitude of the GABAergic projection suggests that it may represent an important inhibitory influence of the descending efferent output from the basal forebrain and preoptic-anterior hypothalamic regions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.