Cortical cells should fire regularly, but do not

When a typical nerve cell is injected with enough current, it fires a regular stream of action potentials. But cortical cells in vivo usually fire irregularly, reflecting synaptic input from presynaptic cells as well as intrinsic biophysical properties. We have applied the theory of stochastic processes to spike trains recorded from cortical neurons (Tuckwell 1989) and find a fundamental contradiction between the large interspike variability observed and the much lower values predicted by well-accepted biophysical models of single cells

The lemniscal–cuneate recurrent excitation is suppressed by strychnine and enhanced by GABAA antagonists in the anaesthetized cat

[Abstract] In the somatosensory system, cuneolemniscal (CL) cells fire high frequency doublets of spikes facilitating the transmission of sensory information to diencephalic target cells. We studied how lemniscal feedback affects ascending transmission of cutaneous neurons of the middle cuneate nucleus. Electrical stimulation of the contralateral medial lemniscus and of the skin at sites evoking responses with minimal threshold induced recurrent activation of CL cells at a latency of 1–3.5 ms. The lemniscal feedback activation was suppressed by increasing the stimulating intensity at the same sites, suggesting recurrent-mediated lateral inhibition. The glycine antagonist strychnine blocked the recurrent excitatory responses while GABAA antagonists uncovered those obscured by stronger stimulation. CL cells sharing a common receptive field (RF) potentiate one another by recurrent activation and disinhibition, the disinhibition being produced by serial interactions between glycinergic and GABAergic interneurons. Conversely, CL cells with different RFs inhibit each other through recurrent GABA-mediated inhibition. The lemniscal feedback would thus enhance the surround antagonism of a centre response by increasing the spatial resolution and the transmission of weak signals.Consejo Interinstitucional de Ciencia y Tecnología; PM99-002

Tonic and bursting activity in the cuneate nucleus of the chloralose-anesthetized cat

[Abstract] Whole-cell recordings were obtained from cuneate neurons in anesthetized, paralysed cats. Stimulation of the contralateral medial lemniscus permitted us to separate projection cells from presumed interneurons. Pericruciate motor cortex electrical stimulation inhibited postsynaptically all the projection cells (n=57) and excited all the presumed interneurons (n=29). The cuneothalamic cells showed an oscillatory and a tonic mode of activity. Membrane depolarization and primary afferent stimulation converted the oscillatory to the tonic mode. Hyperpolarizing current steps applied to projection neurons induced a depolarizing sag and bursts of conventional spikes in current-clamp records. This indicates the probable existence of low-threshold and hyperpolarization-activated inward currents. Also, the hyperpolarization induced on projection cells by motor cortex stimulation deinactivated a low-threshold conductance that led to bursting activity. The presumed cuneate interneurons had larger and more proximally located peripheral receptive fields than the cuneothalamic cells. Finally, experiments specifically designed to test whether motor cortex-induced presynaptic inhibition could be postsynaptically detected gave negative results. These results demonstrate, for the first time, that the cuneothalamic cells possess both bursting and tonic firing modes, and that membrane depolarization, whether produced by injection of positive current or by primary afferent stimulation, converts the oscillatory into the tonic mode.Dirección General de Investigación Científica y Técnica; PB93-034

The influence of nitric oxide on perigeniculate GABAergic cell activity in the anaesthetized cat

[Abstract] We have tested the effect of iontophoretic application of the nitric oxide synthase inhibitor l-nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during l-nitroarginine application (n= 15), the visually elicited responses were markedly reduced, on average by 63 ± 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co-application of the substrate for nitric oxide synthase, l-arginine, but not by the inactive d-isoform, although application of l-arginine alone was without effect. Pressure application of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n= 12). The nitric oxide synthase inhibitor l-nitroarginine was applied to a sub-population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 % 14%) with little or no effect on the excitation mediated by α-amino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) or quisqualate (effects not statistically significant), and it had no effect (n= 7) on excitation mediated by the metabotropic agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the actions Of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and Y type cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co-localized with nitric oxide synthase at both sites). We propose that within the PGN nitric oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non-specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex.Ministerio de Educación y Ciencia; PB93-034

Further observations on the role of nitric oxide in the feline lateral geniculate nucleus

[Abstract] We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L-arginine, but not the biologically inactive isomer, D-arginine. Nitroprusside and S-nitroso-N-acetylpenicillamine (SNAP), nitric oxide donors, but not L-arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.Ministerio de Educación y Ciencia; PB93-034

Sensorimotor cortical influences on cuneate nucleus rhythmic activity in the anesthetized cat

[Abstract] This work aimed to study whether the sensorimotor cerebral cortex spreads down its rhythmic patterns of activity to the dorsal column nuclei. Extracellular and intracellular recordings were obtained from the cuneate nucleus of chloralose-anesthetized cats. From a total of 140 neurons tested (106 cuneolemniscal), 72 showed spontaneous rhythmic activity within the slow (<1 Hz), δ (1–4 Hz), spindle (5–15 Hz) and higher frequencies, with seven cells having the δ rhythm coupled to slow oscillations. The spindle activity recorded in the cuneate was tightly coupled to the thalamo-cortico-thalamic spindle rhythmicity. Bilateral or contralateral removal of the frontoparietal cortex abolished the cuneate slow and spindle oscillations. Oscillatory paroxysmal activity generated by fast electrical stimulation (50–100 Hz/1–2 s) of the sensorimotor cortex induced burst firing synchronized with the paroxysmal cortical “spike” on all the non-lemniscal neurons, and inhibitory responses also coincident with the cortical paroxysmal “spike” in the majority (71%) of the cuneolemniscal cells. The remaining lemniscal-projecting neurons showed bursting activity (11%) or sequences of excitation–inhibition (18%) also time-locked to the cortical paroxysmal “spike”. Additionally, the cerebral cortex induced coherent oscillatory activity between thalamic ventroposterolateral and cuneate neurons. Electrolytic lesion of the pyramidal tract abolished the cortically induced effects on the contralateral cuneate nucleus, as well as on the ipsilateral medial lemniscus. The results demonstrate that the sensorimotor cortex imposes its rhythmic patterns on the cuneate nucleus through the pyramidal tract, and that the corticocuneate network can generate normal and abnormal patterns of synchronized activity, such as δ waves, spindles and spike-and-wave complexes. The cuneate neurons, however, are able to generate oscillatory activity above 1 Hz in the absence of cortical input, which implies that the cerebral cortex probably imposes its rhythmicity on the cuneate by matching the intrinsic preferred oscillatory frequency of cuneate neurons.Dirección General de Investigación Científica y Técnica; PB96-095

Communications Biophysics

Contains reports on three research projects.United States Air Force (Contract AF19(604)-4112

Towards building a more complex view of the lateral geniculate nucleus: Recent advances in understanding its role

The lateral geniculate nucleus (LGN) has often been treated in the past as a linear filter that adds little to retinal processing of visual inputs. Here we review anatomical, neurophysiological, brain imaging, and modeling studies that have in recent years built up a much more complex view of LGN . These include effects related to nonlinear dendritic processing, cortical feedback, synchrony and oscillations across LGN populations, as well as involvement of LGN in higher level cognitive processing. Although recent studies have provided valuable insights into early visual processing including the role of LGN, a unified model of LGN responses to real-world objects has not yet been developed. In the light of recent data, we suggest that the role of LGN deserves more careful consideration in developing models of high-level visual processing