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We consider the construction of optimal molecular descriptors for characterization of the C[dbnd]C bond in alkenes. In particular we consider the use of path numbers and weighted path numbers as molecular descriptors and molar refraction as the molecular property on which the new descriptors are tested.

WOS: 000305806500005, Turkish Scientific and Technical Research Council (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108T566]; Institute of Biology of the Romanian Academy Bucharest [RO1567-IBB03/2012]; CIUNT (Secretaria de Ciencia y Tecnica, Universidad Nacional de Tucuman)Secretaria de Ciencia y Tecnologia (SECYT); CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas)Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Ucka Nature Park; 'Research and Development for Innovations' Operational Programme; European UnionEuropean Union (EU); state budget of the Czech Republic; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [11-04-01247-a]; Polish Ministry of Science and Higher EducationMinistry of Science and Higher Education, Poland [N N 303 796 940, N N 303 469 338, N N 304 028539], Z. Modric Surina, M. Randic,and A. Alegro are grateful to Professor Marko Sabovljevic from Institute of Botany, Faculty of Biology, University of Belgrade (Serbia) for confirming the determination of Calypogeia sphagnicola. The study by T. Ozdemir, N. Batan, and G. Uyar was supported by the Turkish Scientific and Technical Research Council (TUBITAK) with project code 108T566. S. Stefanut, is grateful to J. Vana for confirming the identity of Marsupella boeckii and acknowledges the support by project no. RO1567-IBB03/2012 through the Institute of Biology of the Romanian Academy Bucharest. C.R. Stevenson is grateful to Tom Blockeel for the identification of Orthotrichum schimperi and O. gymnostomum, and to Francisco Lara for confirming O. schimperi. G. M. Suarez thanks Richard Zander for comments and suggestions on his manuscript. His financial support was provided by CIUNT (Secretaria de Ciencia y Tecnica, Universidad Nacional de Tucuman) and CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas). A. Bergamini and A. Cogoni thank Alberto Spinelli for organizing the BRYOLICH excursion to Sardinia and Edi Urmi for help with locality information. The contribution of A. Martincic. and B. Surina was supported financially by Ucka Nature Park. P. Gorski is grateful to Professor Jiri Vana (Charles University, Prague, Czech Republic) for revision of herbarium specimens, and he acknowledges financial support from the Polish Ministry of Science and Higher Education through grant no. N N 304 028539. The contributions by H. Bednarek-Ochyra and R. Ochyra have been financially supported by the Polish Ministry of Science and Higher Education through grant nos. N N 303 796 940 (for H. Bednarek-Ochyra) and N N 303 469 338 (for R. Ochyra). They also thank the Curators at BM and NSW for the loan of the herbarium material. The field work of R. Ochyra and Marc Lebouvier on Iles Kerguelen was organized within programme 136 ECOBIO of the French Polar Institute (IPEV). The contribution by V. Plasek and J. Sawicki is part of a research project of the Institute of Environmental Technologies, reg. no. CZ.1.05/2.1.00/03.0100, supported by the 'Research and Development for Innovations' Operational Programme, and financed by the Structural Funds of the European Union and by the state budget of the Czech Republic. These authors would like to thank O. M. Afonina and L. E. Kurbatova for their kind permission to study herbarium materials in LE. The contributions by L. E. Kurbatova were financially supported by grants from the Russian Foundation for Basic Research (Project 11-04-01247-a).

There is considerable interest in understanding long-term potentiation (LTP) of glutamatergic synaptic transmission because the molecular mechanisms involved in its induction and expression are thought to be essential for learning, memory and pain. The molecular mechanisms involved in induction and expression of LTP have been widely characterized, especially in the hippocampus and have been proposed to be cellular models of learning and memory. LTP in the spinal pain pathways has been considered as one of the cellular mechanisms of post-injury pain hypersensitivity (central sensitization). Extensive evidence has indicated that changes in both the presynaptic release of glutamate and postsynaptic response to glutamate are involved in expression of LTP. This chapter attempts a brief review of some of the postsynaptic mechanisms underlying induction, expression and modulation of the high frequency stimulation-induced LTP of excitatory synaptic transmission in the superficial dorsal horn of the spinal cord. It is becoming clear that the spinal LTP, which might contribute to hyperalgesia in animal models of pain, uses multiple mechanisms involving protein phosphorylation, similar to the processes associated with hippocampal LTP. Modulation of postsynaptic AMPA and NMDA receptor function caused by phosphorylation may play an important role in the induction and expression of synaptic plasticity at dorsal horn excitatory synapses.

The OECD has proposed five principles for validation of QSAR models used for regulatory purposes. Here we present a case study investigating how these principles can be applied to models based on Kohonen and counter propagation neural networks. The study is based on a counter propagation network model that has been built using toxicity data in fish fathead minnow for 541 compounds. The study demonstrates that most, if not all, of the OECD criteria may be met when modeling using this neural network approach.

A snark is a non-trivial cubic graph admitting no Tait coloring. We examine the structure of the two known snarks on 18 vertices, the Blanuša graph and the Blanuša double. By showing that one is of genus 1, the other of genus 2, we obtain maps on the torus and double torus which are not 4-colorable. The Blanuša graphs appear also to be a counter example for the conjecture that the orientable genus of a dot product of n Petersen graphs is n-1 (Tinsley and Watkins, 1985). We also prove that the 6 known snarks of order 20 are all of genus 2.

ITERATIVE LEAST SQUARES PROGRAM FOR GENERALIZED CONNECTIVITY DESCRIPTORS The generalized connectivity ondex for a given pphysicochemical property of molecules associates to different atoms parameters which need to be determined by minimizing the standard error with regard to a learning set ( M.Randić et al., in press). We report a program based on Newton's iterative non linear least square method which starts with experimental values for a number of molecules, their adjacency matrices and an esstimate of ( nonhydrogen) atom parameters. The program calculates the connectivity index, its linear reggression parameters with the physicochemical property and starts an iterative procedure in which the atom parameters are optimized until the best linear regression of the connectivity indeces with the property is obtained. The procedure yields parameters and confidence limits for determination of molecular physicochemical propery values which are either unknown or included in the learning set.

Glutamate-gated ion channels mediate excitatory synaptic transmission in the central nervous system and are involved in synaptic plasticity, neuronal development and excitotoxicity (5,24). These ionotropic glutamate receptors were classified according to their preferred agonists as AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), KA (kainate), and NMDA (N-methyl-D-aspartate) receptors [Trends Pharmacol. Sci., 11 (1990) 25-33]. The present study of NMDA receptor channels expressed in acutely isolated spinal dorsal horn (DH) neurons of young rat reveals that they are subject to modulation through the adenylate cyclase cascade. Whole-cell voltage-clamp recording mode was used to examine the effect of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) on the responses of DH neurons to NMDA. Whole-cell current response to NMDA was enhanced by 8 Br-cAMP, a membrane permeant analog of cAMP or by intracellular application of cAMP or catalytic subunit of PKA.

A graph-theoretical approach lead to a formulation of the necessary structural constraints on a conjugated hydrocarbon system which forms the repeating unit for an aromatic polymer to show conductivity. A procedure for an estimate of the energy gap associated with the conjugated monomer unit has been described. It allows evaluation of the associated determinants simply and without performing the actual lengthy expansions. It is based on corresponding graph decompositions. The approach is illustrated on several selected benzenoid hydrocarbons. General rules covering a wide range of polymers which are potentially conductive are given. They are based on the structure of the single repeating unit and the corresponding graph-theoretical characterizations. The approach may facilitate further search for organic potential semiconductors.

This paper is the first in a series concerned with a particular graph theoretical scheme for enumeration and derivation of structures of prescribed form. The problem spoken to by this work is that of finding a unique formal procedure for generating all distinct (i.e. non-isomorphic) graphs of a given number of vertices and prescribed valency. Here the scheme is outlined as applied to a search for regular trivalent graphs, some of which correspond to trivalent polyhedra. A systematic procedure for obtaining the number of equivalence classes of the adjacency matrices associated with trivalent graphs of n points is described. The procedure is of general applicability, though no proof of its correctness is offered. Instead, a number of examples are discussed, and its application is illustrated. The scheme is based on consideration of unique matrices associated with graphs which in turn are determined so that the corresponding binary code obtained by reading the rows of the matrix from left to right and from top to bottom represents the smallest possible binary code. Part of the scheme consists in finding all acceptable matrices, testing them for isomorphism, and selecting those which satisfy additional restrictions and ensure that the derived graph represents a structure of interest.

Algorithms for making Kekule-structure and algebraic-structure enumerations for unbranched catacondensed hydrocarbons with even-membered rings are described. A pictorial presentation of the algorithms is obtained and is shown to reduce to an earlier well-known recursion (of Gordon and Davison) applicable to polyhex chains.

Structural indices which characterize individual benzene rings in benzenoid hydrocarbons have been suggested. For each ring separately we count the number of classical valence structures in which the ring is formally represented by a Kekule benzene formula. The ratio of this number and the total number of classical valence structures for the molecule is suggested as a measure of benzenoid-like character of the ring considered. Rings with local indices approaching one, the value belonging to benzene, correspond to more isolated pi-electron sextets, those with an intermediate values indicate more delocalized environment. Rings with very small indices, approaching zero or being zero, are typical for rings not contributing to conjugation significantly. Limited experimental evidence is consistent with the concept of local ring character as illustrated by a correlation between Me doublet separation in NMR spectra of selected dimethyl substituted polycondensed benzenoid hydrocarbons. The sum of the contributions of all rings constitute a molecular index of benzenoidity which can serve as a topological measure of molecular aromaticity.

Properties of molecular graphs having identical topological spectra are investigated in some detail. It has been established that whole families of isospectral graphs can be derived from a molecular skeleton of vinyl benzene. A pair of isospectral graphs are obtained by an exchange of two non-equivalent residuals attached to particular sites of the skeleton. Additional pairs of isospectral graphs can be derived from related skeletons in which ortho positions of vinyl benzene are occupied by substituents. No constraints have to be imposed on the nature and form of the residuals or the substituting groups. This allows construction of larger isospectral systems including polymeric species. The theoretical foundation for the construction of isospectral graphs described in this work rests on the factorization of the eigenvalue problem of the adjacency matrix associated with molecular graphs which is analogous to a fragmentation of a secular determinant of a Huckel MO problem as outlined some time ago by Heilbr...

The H + 2 ground state energy is calculated over the range of internuclear separation from R = 0.2 au to R = 8.0 au, using a Laplace transform-type wave function. The integral transform is made on Slater-type functions with the weighting function f (ν, p , α) = α (ν+3)/2 exp (− p α/2). The electronic energy E = −1.0833 au for the equilibrium internuclear distance ( R = 2.0 au) is obtained with incomplete optimization. Still lower energy is expected for larger values of the parameters v and p . The difference between the calculated and the exact energies is not excessive over the whole range of internuclear separations considered.

The electrostatic point charge model of the ligand field theory is extended by representing each ligand by 2635 points uniformly distributed at the position of the ligands. Application to a square planar, trigonal bipyramidal and octahedral structure is considered. The orders of d-orbitals are found to be the same as those based on the simple point charge model, for the examples examined. However, the centre of the splitting is at somewhat higher values in the diffuse charge model and the overall magnitude has decreased. Moreover the relative magnitude of the separation of individual d-orbitals has also been altered. The diffuse charge model thus introduces new features which merit attention.

The hybridization in cyclopropane, spiropentane, nortricyclene and 1,1 -dimethyl cyclopropane is calculated applying the criterion of maximum overlap. The s-p content in the general hybrids is found to be sensitive to changes in the interorbital angle Θ ij. The results give information about the strain associated with bent bonds and its delocalization. The application also allows calculations of skeletal angles, such as ∢ C1 C2 C3 in nortricyclene, which determine the geometry of the molecule.

The hybridisation in cyclopropene, cyclobutene, 1-methylcyclobutene, and 3-methylcyclobutene, all containing a double bond in the ring, is considered by applying the method of maximum overlap. The results show a considerable increase in s-contribution for the hybrids forming the double bond. The participation of s-orbitals in the hybrids forming the double bond is larger in cyclobutene than in cyclopropene, an indication that the preference for s-character will be even more pronounced in strain-free systems. The calculated bond overlaps are compared with the experimental bond energies. Instead of assuming the simple proportionality when scaling an overlap, a general linear relationship E=kS–l must be used.

High resolution infrared spectra of gaseous methyl silane were obtained and a complete assignment of vibrational frequencies has been made. The methyl rocking and silyi deformation bands were distinguished with the help of the Coriolis zeta constants. Normal co-ordinates and zeta constants were calculated on the basis of a simple diagonal potential function.

The construction of hybrids in electron deficient systems of given geometry is discussed. Molecular orbitais obtained by applying the criterion of maximum overlap, as developed by Lykos and Schmeising, are given for CH 5 + (assuming a trigonal bipyramidal structure) and B 2 H 6 . Two electron-three center bonds for axial CH bonds, or alternatively a degenerate ( E class) four electron-four center bonding for equatorial CH bonds are obtained. In diborane the familiar two electron-three center bonds involving bridge hydrogen result. Maximum overlap molecular orbitals for diborane are similar to those of the SCF calculation, indicating the usefulness of applying simple overlap calculations to related larger electrondeficient systems.

For some thirty hydrocarbons the s character of hybrids obtained by the application of the maximum overlap method have been correlated with C-H and C-C spin-spin coupling constants. The following relationships were obtained: $$J_{{\text{C}}^{{\text{13}}} - {\text{H}}} = 1079a_{{\text{CH}}}^{\text{2}} /(1 + S_{{\text{CH}}}^{\text{2}} ) - 54.9$$ , $$J_{{\text{C}}_{\text{1}}^{{\text{13}}} - {\text{C}}_{\text{2}}^{{\text{13}}} } = 1020.5a_{{\text{C}}_{\text{1}} }^2 a_{{\text{C}}_{\text{2}} }^{\text{2}} /(1 + S_{{\text{CC}}}^{\text{2}} ) - 8.2$$ . Here the coupling constants are expressed in cps units. In the calculation of the maximum overlap hybrids either the experimental bond lengths or a standard bond lengths were used. For the $$J_{{\text{C}}^{{\text{13}}} - {\text{H}}}$$ and $$J_{{\text{C}}^{{\text{13}}} - {\text{H}}} $$ coupling constants the standard deviations are 0.9 cps and 1.9 cps respectively. It has been suggested that the large additive constant in the $$J_{{\text{C}}^{{\text{13}}} - {\text{H}}}$$ correlation may be attributed to the ionic character of C-H bonds. A good agreement with the experimental data strongly supports the idea that the Fermi contact term and the hybridization are dominant factors in determining carbon-hydrogen and carbon-carbon spin-spin coupling constants across one bond, at least in hydrocarbons.

A generalization of the Kekule index for composite valence structures provides a quantitative value corresponding to Clar's assessment of benzenoid character of aromatic ring systems. The idea involved is further specialized for the individual local rings in the molecules. Comparison with limited experimental data supports the validity of this approach.

The simple electrostatic point charge model of the ligand field theory is extended by representing each ligand by N fractional point charges. The special cases N=6,18, and 62 are considered. A spherical charge distribution gives results similar to those of the point charge model. The splittings for non-spherical charge distributions are found to depend strongly on the orientation of the ligand charge.

The hybridization in methylenecyolopropane, dimethylenecyclopropane, bisethanoallene, and related molecules containing double bonds externally attached to a cyclopropane ring is considered by applying the method of maximum overlap. The results show that the bond overlap of an exocyclic double bond is larger than the bond overlap of a normal C=C bond, and double bonds in allenes have even larger overlap than an exocyclic C=C bond. The results of the calculations are correlated with some available experimental data.

SummaryWhole-body x-irradiation with high doses produces an increase in the 5-hydroxytryptamine-content in the brain of normal rats and mice. This effect was obtained with smaller doses only in adrenalectomized rats. Shielding of the head or body did not suppress this phenomenon. The same holds true of pre-treatment with iproniazid or reserpine.

The distribution of s and dcharacter of general snp3d5−n hybrids describing eight-coordinated square antiprism complexes is investigated. It is found that the participation of dz2 in hybridization depends critically on the magnitude of the ratio of metal-ligand orbital overlaps. Several complexes of rhenium, thallium, tungsten and zirconium are discussed. Hybrids of the form s 1 2 p3d 0 2 approximately describe all the individual cases and may well represent a typical hybridization for the first- and second-row transition metals in complexes of the square antiprism structure.

The splittings ofd-orbitals for seven coordinated complexes of the type NbF7 2− is calculated using a point charge model. The perturbed energies are expressed as a function of λ =G 2/G 4. The results are very sensitive on assumed geometrical angles of the molecule.

The hybridization in cyclobutane, bicyclobutane, 1,3-dimethylcyclobutane, 1,3-dimethylbioyclobutane, bicyclo(1.1.1)pentane, tricyclo(1.1.0.02,4)butane, cubane and tetracyclo-(3.3.1.02,804,6)nonane is considered applying the method of maximum overlap (Tab. 1). Overlap seems to be a good index of a CC bond: overlaps below 0.6000 are characteristic for molecules containing C3-ring (δ ∼ 20‡), between 0.6000 and 0.6300 for four membered ring (δ ∼ 10‡), and above 0.6300 for normal or very slightly bent bonds (δ

A general theory is given of the intermolecular energy when there is small overlap between orbitals of different molecules. The energy is expanded as a power series in the intermolecular potential U and the overlap integral S , and expressions are given for the contributions to the energy up to order U 2 S 2 . We have defined exchange energy by the contribution of order U S 2 . This leads to a simpler expression than the more familiar valence-bond definition of the term. The energy contributions of order U 2 S 2 may be subdivided into two parts, exchange polarization energy and charge transfer energy. The mathematical validity of this subdivision is discussed.

The splitting and the order of 3d- and 4d-orbital energies for some complexes of the first- and second-transition series having dodecahedral geometry is calculated by the simple crystal-field model. The relative order of energy levels depends on the nature of the ligands and their distances from the metal. The energy behaviour is further examined as a function of the ratio G2 : G4 by assuming first all ligands equal and at the same distance from central metal, and then for cases when all ligands are equal but at different distances from the central metal. The discussion is extended to cases when different ligands are present in the complex. The results suggest that there is no representative energy diagram valid for all MX8 dodecahedral complexes. The calculations are applied to some complexes of Zr, Mo, Ti, Cr, and Co in order to illustrate the variations met in actual cases. It is found that dxy is the most stable for 4d and dz2 for 3d complexes examined.

Excitability of testing of single sural afferent C- and A-fibers was used to study possible presynaptic actions of substance P (SP) applied locally or systemically at the in traspinal sites of minimal threshold for their antidromic activation in anesthetized or spinalized cats. SP, applied by iontophoresis, pressure microinjection or systemically, produced dose-related reversible decreases or increases in threshold for antidromic activation of both C- and A-fibers. It was concluded that, in addition to previously shown postsynaptic actions, SP modifies excitability of intraspinal cutaneous C- and A-fibers.

It is shown how two-center electron-repulsion integrals of hybrid type can be reduced to linear combinations of overlap integrals. In certain cases the overlap integrals involve orbitals whose principal quantum numbers are less than their azimuthal quantum numbers. Explicit formulas are presented for the reduction of all hybrid integrals containing only orbitals of principal quantum numbers 1 or 2.

String comparison techniques were developed and applied for measuring the molecular similarity of chemical structures. The molecular structures were encoded as a sequence of numbers representing counts of paths of different lengths. The similarity index between two compounds was calculated as the difference between the gains of information derived through comparison of the corresponding molecular path sequences. Ranks between the structures of the studied data base obtained according to this similarity were used as basic data for deriving correspondences between the elements of the set of compounds. The method was applied on a group of 41 barbiturates. Correlation equations were calculated for different groups of compounds grouped according to the displayed similarity. The correlation equations and the corresponding statistics were obtained using standard computer programs. Special algorithm for computing the similarity index and the correlation matrix (outlined very briefly) was developed and implemented on VAX 11/750.

Recently (Chem. Phys. Lett. 42 283 (1976) a simple procedure for deriving symmetry properties of graphs has been suggested. It is based on a canonical numbering of the vertices of a graph, and consists in searching for all the acceptable numberings which have a unique adjacency matrix. In the series of papers initiated here we will apply the above procedure and derive all symmetry operations for graphs of interest to chemistry. We start with the Petersen graph which is of interest in discussions of isomerizations of trigonal bipyramidal structures.

Enumeration of valence structures for conjugated radical cations is of interest in estimating the first ionization potentials of conjugated hydrocarbons. Alternative routes for enumeration are reviewed and a novel method, based on the properties of the acyclic polynomials of conjugated structures, is outlined. The method is illustrated for several molecules and results reported for a number of conjugated systems involving either 14 or less carbon atoms.

An approach based on graph theoretical methods for searching the most potent drug among numerous candidate structures is outlined. First, we identify the strategic fragment and describe it by suitable graph theoretical invariants. We have adopted path numbers derived from suitably weighted bonds as basic invariants. Similarity among structures is quantitatively derived from similarity and differences in atomic path numbers for the strategic fragment. The approach is illustrated on a selection of antitumor phenyldialkyltriazenes for which log(1/C) are known. By starting the search with an unsubstituted parent compound, in few steps we located 1-(4-NHCOCH3-Phenyl)-3,3-dialkyltriazene as the most potent drug among those considered.

Recently structural features which characterize the energy gap in polymeric conjugated hydrocarbons within the framework of the simple Hiickel MO theory have been specified using graphtheoretical methods. It has been shown that molecules of interest as potential units in polymers with zero energy gap have to satisfy certain structural conditions which relate the number of selected »excited« valence structures to that of the Kekule structures for the system. As in the previous work we consider units separated by essentially single bonds. Here we elaborate on the search for benzenoid systems which can satisfy the requirement. A necessary condition that a system may have zero energy gap is that the repeating benzenoid unit has a non-prime number (K) of Kekule valence structures. Then K could be factored: K1 • K2 ... Km. (Generally, there are more factorizations of K and our procedure needs to be carried out over all of them). Fragments Fi that have the number of Kekule structures given by K; are recognized, and we try to superimpose all of them over the skeleton of monomer unit. (Our procedure needs to be carried out for all possible fragmentations corresponding to a given factorization) . If it is possible to cover the monomer unit with all the fragments leaving at least two positions available for linking the units in polymer form, then the energy gap of such a polymer is zero. In a number of examples it is illustrated how the actual search is performed. A list of benzenoid systems of interest as units in a polymer with zero energy gap is given. The search is quite efficient and speedy.

An additivity scheme, based on Clar's formulae, is proposed for calculating heats of atomization of benzenoid hydrocarbons: Comparison between the results obtained by this scheme, by the semiempirical SCF MO model, and experimental findings is good. This satisfactory agreement, thus, presents independent support for Clar's notion of isolated Jt sextets and migrating sextets.

It has been shown that topological spectrum of some large molecules comprises the complete set of eigenvalues of the topological matrix of some of their constituting fragments. Several relationships between the coefficients of the fragmental eigenvectors and those of the composite system have been derived. Some sufficient conditions that a system comprise a spectrum of its parts have been found and their use illustrated.

High intensity repetitive stimulation of a dorsal root elicited slow depolarization in more than half of the dorsal horn neurons examined in the rat spinal cord slice preparation. There was a significantly smaller group of neurons showing slow hyperpolarization as well. Slow depolarization was not observed when synaptic activity was blocked by perfusing the slice with a TTX- or a low-Ca2+ high-Mg2+ solution. This result is consistent with a presynaptic origin of the slow response. Capsaicin treatment of neonatal rats significantly reduced the incidence of slow depolarization, suggesting that the slow depolarization was generated by small diameter afferent fibres, probably unmyelinated afferents. DR-evoked slow depolarization and SP-induced depolarization were similar in several important aspects: a) Both responses caused depolarization and increased the excitability of dorsal horn neurons; b) They were frequently associated with similar membrane conductance changes; c) The size of both responses varied in parallel when the membrane potential was shifted over a wide range; d) Both responses were markedly reduced or abolished by an analogue of SP having antagonist properties, and by polyclonal and monoclonal antibodies to SP; e) The depression of the DR-elicited slow depolarization during and after the SP-induced depolarization suggested that SP and the natural transmitter for the DR-elicited slow depolarization were bound to the same receptors. The results suggest that SP or, SP-like peptide, is an agonist that mimics in some aspects the action on the natural transmitter for the slow depolarizing potential.

This work represents an attempt to elucidate structural features of electrophysiologically characterized, individual cat dorsal spinocerebellar tract (DSCT) neurons by using intracellular application of horseradish peroxidase (HRP). Intracellular recordings and HRP injections were made in DSCT neurons of the Clarke's column in cat lumbar (L3) spinal cord. The units were identified by antidromic invasion following electrical stimulation of the ipsilateral dorsolateral funiculus at C1. In addition, sensory inputs to the DSCT neurons were determined by natural (adequate) stimuli applied to the hind limb with intact innervation. The morphological analysis is based on data obtained from 19 well-stained electrophysiologically identified neurons located in Clarke's column. Thirteen of these units received excitatory sensory inputs from muscle receptors, two were activated by cutaneous afferents only, and four had a convergent (muscle + cutaneous) input. The DSCT--muscle cells were equivalent to the large Clarke cells (class C of Leowy, '70). Their dendrites were oriented primarily in the rostro--caudal direction (up to 2500 micron) and appeared generally smooth except for some branchlets. In four of these cells, the axon was traced into the lateral funiculus. In light microscopic analysis there was no evidence that axon collaterals arose from these axons during the initial trajectory through the spinal grey matter. The four DSCT--convergent neurons were similar in shape to the DSCT--muscle units although they appeared to have somewhat smaller cell bodies. Of the two DSCT--cutaneous neurons one was found to be of the B type, with the dendritic tree having fewer branches and oriented mainly in the medio--lateral direction. The other cell, however, turned out to be similar in appearance to the C type Clarke neurons.

1. The responses of identified cells in the cat Clarke's column and dorsal horn to micro-electrophoretically applied cholinomimetics and anti-cholinergic substances have been investigated. 2. Both antidromically identified (DSCT neurones) and synaptically activated neurones from the region of the Clarke's column of the spinal cord were excited by ACh. However, the proportion of ACh excited cells was greater in units synaptically activated by ipsilateral dorsolateral funiculus stimulation (78%) than in DSCT neurones (50%). In addition, about 55% of neurones activated either antidromically or synaptically by ipsilateral dorsal column stimulation were excited by ACh. 3. In contrast to a relatively weak excitatory potency on the DSCT neurones (maximum firing frequency did not exceed 130% of the control activated by ipsilateral dorsolateral funiculus stimulation (maximum firing frequency reached 430% of the control level). 4. ACh has a relatively quick and rapidly reversible excitatory effect on Clarke's column neurones and some types of dorsal horn interneurones, which can be obtained also with nicotine. However, the action of nicotine is frequently delayed in onset and recovery. This excitatory action of ACh can be blocked or markedly depressed by dihydro-beta-erythroidine. These results and those obtained with acetyl-beta-methylcholine and atropine seem to suggest that the receptors mediating excitation of the cholinoceptive spinal cells activated either antidromically or synaptically by ipsilateral dorsolateral funiculus stimulation besides predominantly nicotinic have also weak muscarinic properties. 5. Desensitization with repeated applications of ACh and nicotine has been observed in both DSCT neurones and units antidromically activated by ipsilateral dorsal column stimulation. 6. About 11% of units antidromically activated by ipsilateral dorsolateral funiculus stimulation were depressed by ACh. In addition, the depressant effect of ACh was more frequently encountered in the cells unresponsive either to the dorsolateral funiculus or dorsal column stimulation. ACh depression was also seen in units activated either antidromically or synaptically by ipsilateral dorsal column stimulation. In contrast, none of the units synaptically activated by the ipsilateral dorsolateral funiculus stimulation were depressed by ACh. The same was true for spinal neurones receiving convergent peripheral inputs activated either antidromically or synaptically by ipsilateral dorsolateral or dorsal column stimulation. 7. The findings that ACh depression of all tested DSCT neurones is blocked by atropine and readily evoked by acetyl-beta-methylcholine indicates that receptors mediating the effect are of muscarinic type.