Lex C. Towns

Functional Trade-Offs in White Matter Axonal Scaling

The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1–5 ms across the neocortex and <1 ms from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 ± 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time.

The head-twitch response in the least shrew (Cryptotis parva) is a 5-HT2− and not a 5-HT1C-mediated phenomenon

Our initial studies suggested that the 5-HT2/1C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane [(+/-)-DOI] produces both the head-twitch response (HTR) and the ear-scratch response (ESR) in mice via stimulation of 5-HT2 receptors. However, challenge studies revealed that these behaviors are produced via two different receptors (possibly 5-HT2 and 5-HT1C). Due to a lack of selective agents one cannot designate a particular response for the activation of a specific receptor. The purpose of the present study was to investigate such behaviors in the least shrew, which is more sensitive to (+/-)-DOI than rodents. IP injection of (+/-)-DOI in shrews produced a dose-dependent (bell-shaped) and time-dependent increase in the HTR frequency. The (+/-)-DOI-induced HTR was equipotently and completely attenuated by the 5-HT2/1C antagonists ketanserin and spiperone. The 5-HT1C antagonist with 5-HT2 agonist action, lisuride, also produced the HTR in a bell-shaped dose- and time-dependent fashion. Central injections of both (+/-)-DOI (0.2 microgram) and lisuride (0.5 microgram) also induced the behavior. Both peripheral and central administration of lisuride failed to produce the ESR. (+/-)-DOI significantly induced the ESR only at the highest dose tested (2.5 mg/kg, IP). Centrally administered (+/-)-DOI (0.2 microgram) produced more ESRs relative to vehicle controls; however, the difference did not attain significance. At low doses (0.31 and 0.63 mg/kg), (+/-)-DOI had no effect on locomotor activity, but it significantly attenuated the behavior at larger doses. Both low and high doses of lisuride increased the motor activity. Spiperone dose-dependently suppressed locomotion, whereas ketanserin had no effect. The present results suggest that the HTR is a 5-HT2 receptor-mediated event and changes in locomotor activity do not affect the induced HTR.

A Review of Axon Collateralization in the Mammalian Visual System

Axon collateralization appears to represent a prominent feature of the mammalian visual system. Both anatomical and electrophysiological evidence reveal that axon branching occurs in the retinofugal, geniculocortical and visual corticifugal projections. Most of this evidence is provided by studies on the cat, but enough data are available from investigations on the rat and monkey to permit certain interspecies differences to be recognized and evaluated. Axon branching allows individual axons to provide innervation to two or more targets and generally to transmit the same type of visual information to these targets. There is abundant evidence to suggest that two of the three functional classes of retinal ganglion cells and geniculate relay cells (namely Y and W ganglion and relay cells) utilize axon branching; however, few details regarding this subject are currently available. The third functional class of ganglion and relay cells (X ganglion and relay cells) essentially lacks axon branches. This review has three primary goals: (1) to review the pertinent anatomical and electrophysiological literature dealing with axon branching and to discuss areas in which information is meager and further investigation necessary; (2) to emphasize the need for applying recently developed techniques, such as double-labeling of neurons and electrical collision, to the study of axon collateralization, and (3) to formulate some hypotheses concerning the functional significance of axon branching.

Visual receptive-field characteristics of posterior thalamic and pretectal neurons in the rabbit

Summary Receptive fields were determined for 309 cells recorded from the posterior thalamus of 42 Dutch belted rabbits. The responses of the cells to visual stimulation were classified according to receptive field configuration and trigger features as being one of several types: (1) oriented direction-selective, (2) oriented, (3) concentric, (4) direction-selective, (5) movement-sensitive, (6) uniform, (7) diffuse, or (8) no response. Neurons located within nuclei or portions of nuclei which receive a direct projection from the retina (lateral geniculate, dorsal layers of the superior colliculus, dorsal portion of the posterior thalamic nucleus, and dorsal portion of the pretectal nucleus) had highly specific receptive field characteristics,i.e., the first 5 types. Neurons located within areas which do not receive direct retinal projections, but do not receive visual projections from the superior colliculus and visual cortex (ventral layers of the superior colliculus, ventral portion of the posterior thalamic nucleus, ventral portion of the pretectal nucleus, lateral posterior nucleus, and dorsal medial geniculate nucleus) had much less selective receptive fields,i.e., the last 3 types. Neurons in regions receiving only indirect visual projections showed rapid adaptation or habituation to repeated sensory stimulation, while those located in the direct retinal pathway did not. Responses to auditory or somatosensory stimulation were recorded from cells in the indirect visual areas only.

Location of the cutaneous trunci motor nucleus in the dog.

Using the methods of muscle injection of horseradish peroxidase (HRP) and application of HRP to the proximal stump of the cut lateral thoracic nerve (LTN), the motor nucleus of the cutaneous trunci muscle (CTM) has been located predominantly in C8 and T1 spinal cord segments in the ventral and ventrolateral nuclei of Rexeds Lamina IX. Cells of the nucleus are somatotopically arranged rostro-caudally to correspond to the rostro-caudal segmentation. There was a higher average number of HRP-filled cells per section and greater rostro-caudal extent of the nucleus for the cut nerve technique than for the muscle injection technique. Evidence is presented that the CTM is an appendicular muscle in spite of its obvious axial position on the trunk.

Visual receptive-field characteristics of superior colliculus neurons after cortical lesions in the rabbit.

Abstract The responses of 146 neurons recorded from the superior colliculus of the rabbit were classified as belonging to one of eight groups as determined by the spatial configuration of their receptive fields and their trigger features. Seventy of these neurons were obtained from rabbits prepared by ablation of cortex exceeding all known visual areas. This operation did not produce the loss of any receptive field class or trigger feature.

Studies on the Mechanism of the Epileptiform Activity Induced by U18666A. II. Concentration, Half‐Life and Distribution of Radiolabeled U18666A in the Brain

Summary: The concentration, half‐life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 times 10‐6 M and higher were reached soon after giving an acute 10‐mg/kg dose (i.p. or s.c.) of U18666A containing 7‐3H‐U18666A of known specific activity. A steady state concentration of 1 to 2 times 10‐6 M was reached with chronic injection of 10 mg/kg every 4th day, a treatment schedule that results in altered brain lipids and induction of epilepsy if begun soon after birth. The disappearance of U18666A from both brain and serum was described by two similar biexponential processes, a brief rapid clearance (t1/2= 10 h) and a sustained and much slower one (t1/2= 65 h). Brain levels of the drug were about 10 times higher than serum at all times examined. Few differences were seen in the regional distribution of radiolabeled drug in brain as determined by both direct analysis and by autoradiographic examination; but the drug did concentrate in lipid‐rich subcellular fractions. For example, the synaptosome and myelin fractions each contained about 25–35% of both the total 3H‐labeled drug and total lipid in whole brain. The lipid composition of these fractions was drastically altered in treated animals. In conclusion, the chronic epileptiform state induced by U18666A does not appear to involve localization of the drug in a specific brain region or particular cell type. Rather, the condition could involve localization of the drug in lipid‐rich membranes and marked changes in the composition of these membranes.

Termination of thalamic intralaminar nuclei afferents in visual cortex of squirrel monkey

The projection of the thalamic intralaminar nuclei (ILN) upon the visual cortex in the squirrel monkey was studied using anterograde, autoradiographic techniques. In area 17, the ILN afferents terminate in the inner and outer portions of lamina V, whereas in areas 18 and 19 the fibers terminate more diffusely along the laminae V-VI boundary. Widespread labeling of layer I is seen throughout the occipital cortex.

Is there morphological separation between the spinal cord motor nuclei which innervate the heads of a multiheaded muscle

Horseradish peroxidase was injected into the individual heads of the pectoralis muscles of the dog or applied to the nerve which supplies each of these heads. The location and numbers of labeled motoneurons in the spinal cord were studied using light microscopy. There was longitudinal overlap of the pectoral nuclei, but no separation in their mediolateral or dorsoventral positions. The cutaneous trunci muscle motor nucleus is distinctly separate from the motor nuclei of the pectoral muscles, even though they share a common nerve supply. The methods of horseradish peroxidase application to the cut nerve or injection into the muscle are compared.

1,3‐dinitrobenzene toxicity in the least shrew, Cryptotis parva

Shrews are abundant in most areas of toxic chemical contamination and bioaccumulate pollutants at much higher rates than sympatric rodent species. As a part of studies to provide information concerning the toxicity of 1,3-dinitrobenzene (DNB) in least shrews (Cryptotis parva), groups of 10 females and 10 males received DNB at 0 (control), 0.7, 2.9, 11.6, and 46.3 microl/L (equivalent mean daily dosage of 0, 0.26, 1.06, 4.26, and 17.0 mg/kg body wt in each sex) in their diet for 14 d. Leukocytosis present at the 0.26 mg/kg body weight/d dosage established the lowest-observed-adverse effect level (LOAEL). Adrenal enlargement was noted at the 1.06 mg/kg body weight/d level. Splenic enlargement and reductions in hematocrit and hemoglobin values occurred at the 4.26 mg/kg body weight/d treatment. Enlargements in the liver and heart and reductions in brown fat weight, granulocyte numbers, and alanine aminotransferase levels were present at high dose levels. Histopathologic examinations showed Kupffers cell hemosiderosis and suggested testicular damage at the two highest tested doses but failed to confirm brain lesions. Least shrews do not follow standard scaling estimates for lifespan or metabolic rates. The LOAEL calculated from the standard terrestrial screening benchmark equation was higher than our findings, suggesting that these estimates must be viewed with caution.