Stephen E. Fish

Postnatal blockade of cortical activity by tetrodotoxin does not disrupt the formation of vibrissa-related patterns in the rat's somatosensory cortex.

Neuronal activity has been shown to influence pattern formation in the visual system. In the present study, we determined whether or not this was also true in the somatosensory system by silencing the primary somatosensory cortex of rats with tetrodotoxin (TTX) for the first 7-11 days of life. Application of TTX during this period did not prevent the formation of the normal vibrissa-related pattern in S-I as visualized by either staining cortical sections for cytochrome oxidase, demonstration of the pattern with an antibody directed against serotonin, or labelling of thalamocortical axons with the carbocyanine dye, Di-I. These results indicate that neither peripherally evoked nor spontaneous activity are required for qualitatively normal pattern formation in the rats primary somatosensory cortex.

Effects of postnatal blockade of cortical activity with tetrodotoxin upon lesion-induced reorganization of vibrissae-related patterns in the somatosensory cortex of rat

Previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissae-related patterns. In the present study, blockade of cortical activity with TTX was combined with ablation of a row of vibrissae follicles or transection of the infraorbital nerve (ION, the trigeminal nerve branch that supplies the vibrissae follicles) to determine whether the cortical reorganization that follows these lesions in otherwise untreated animals was dependent upon neuronal activity that could be blocked with TTX. The results demonstrated that cortical TTX implants had no quantitative or qualitative effects upon the cortical reorganization that followed either vibrissae follicle cauterization or ION transection.

Organization, Development and Enucleation‐induced Alterations in the Visual Callosal Projection of the Hamster: Single Axon Tracing with Phaseolus vulgaris leucoagglutinin and Di‐l

The distribution of callosal axons interconnecting lateral area 17 and medial area 18 of the rodents occipital cortex is dramatically altered by neonatal enucleation, but it is not known how this manipulation affects the morphology of individual callosal axons or whether the enucleation‐induced changes in this pathway reflect maintenance of a transient developmental state by these fibres. In the present study, these questions were addressed by tracing the individual callosal axons in normal adult and neonatally enucleated adult hamsters with Phaseolus vulgaris leucoagglutinin (PHAL) and by anterograde labelling of developing callosal axons with the carbocyanine dye, Di‐l. In normal adults, injections of PHAL into the region of the 17–18a border produced dense labelling in all layers in the region of the contralateral 17–18a border. Larger injections resulted in callosal labelling that extended across the lateral one‐half of area 17, primarily in layers l and V. Thirty‐four callosal axons from normal adult hamsters were reconstructed through all the cortical laminae. Most of these had very simple terminal arbors. They gave off short collaterals in the infragranular layers and branched more extensively in the uppermost part of layer II‐III and in lamina l. Small injections of PHAL into the occipital cortex of neonatally enucleated adult hamsters resulted in labelled axons throughout most of areas 17 and 18a in the contralateral hemisphere. The terminal arbors of most individual callosal axons in eyeless hamsters were not appreciably different from those in sighted animals. However, 26.8% of 28 fibres reconstructed through all cortical laminae in the neonatally enucleated hamsters had much more widespread branches than any of the axons recovered from normal hamsters. As a result, the average total length of the callosal axons from the blinded hamsters was significantly greater than that for such fibres from the sighted animals. Anterograde labelling with Di‐l demonstrated axons in the anterior commissure and anterior part of the corpus callosum on P‐O. Labelled fibres extended into the white matter underlying the occipital cortex on P‐1 and entered the cortical plate on P‐2. Some of these axons reached into the marginal layer. Many developing callosal axons had short branches in the white matter, but generally extended only a single collateral into the cortical grey matter. Callosal axons in perinatal animals branched very little within the cortex and, in this respect, resembled fibres labelled with PHAL in adult hamsters. These results support the conclusion that the expanded tangential distribution of the occipital callosal projection in neonatally enucleated adult hamsters results, at least in part, from individual axons with abnormally widespread terminal arbors which are not present in large numbers at any time during normal development.

Effects of Postnatal Blockade of Cortical Activity with Tetrodotoxin upon the Development and Plasticity of Vibrissa-Related Patterns in the Somatosensory Cortex of Hamsters

Several previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissa-related patterns in the primary somatosensory cortex of rats. One limitation of these studies is that this pattern forms very shortly after birth in rats, and there may be only a very limited time over which it may be influenced by activity blockade. In the present study, the effect of activity blockade was evaluated in a more altricial rodent, the hamster. The present study showed that a pattern of thalamocortical afferents corresponding to the vibrissae is not observed until the fourth postnatal day in hamsters. Nevertheless, application of TTX-impregnated implants to the cortices of newborn hamsters had no qualitative or quantitative effect upon vibrissa-related patterns in the primary somatosensory cortices of these animals. Moreover, TTX implants did not prevent the changes in patterns that followed cauterization of a row of vibrissa follicles.

Development of the occipital corticotectal projection in the hamster

SummaryAnterograde and retrograde labelling with the carbocyanine dye, Di-I, was used to assess the development of the visual cortical projection to the superior colliculus (SC) in pre- and postnatal hamsters. Posterior cortical axons arrive in the SC on postnatal (P-) day one (the first 24 hours after birth = P-0) and begin to arborize in the superficial laminae (the stratum griseum superficiale [SGS] and stratum opticum [SO]) within one day after they enter the tectum. Over succeeding days, the density of the projection increases and numerous labelled fibers are visible throughout the depth of the SGS and SO. Beginning on P-6, there is a decrease in the density of labelled fibers in the upper SGS and by P-10, the laminal distribution of the occipital corticotectal pathway appears adult-like. Anterograde tracing with Di-I also revealed the presence of a few corticotectal fibers that crossed the midline in both the SC and posterior commissures to terminate mainly in the superficial tectal laminae contralateral to the injection site. Crossed corticotectal fibers were visible in hamsters aged between P-3 and P-12. Retrograde tracing with Di-I in hamsters killed between P-3 and P-12 demonstrated that both the ipsilateral and crossed corticotectal projections arose exclusively from pyramidal cells in developing lamina V.

Differential Effects of Peripheral Manipulations on Vibrissae- Related Patterns in the Trigeminal Brainstem

The expression of galanin and neuropeptide Y (NPY) by primary afferent neurons, including those in the trigeminal (V) system, is markedly up-regulated after peripheral nerve damage and might be expected to influence the response of central somatosensory cells to such damage. In the present study, we assessed the effects of four manipulations that have been used to study development and maintenance of vibrissae-related patterns in the V system-nerve transection, whisker clipping, activity blockade with tetrodotoxin (TTX), and axoplasmic transport attenuation with vinblastine-upon the expression of galanin and NPY by V ganglion cells and their central axons in the V brainstem complex. Both neonatal transection of the infraorbital nerve (ION) and application of vinblastine to it resulted in a marked up-regulation of galanin and NPY in V ganglion cells and their central axon arbors in animals killed on postnatal day 6. Neither whisker clipping nor application of TTX to the ION produced such changes. Both ION transection and application of vinblastine to this nerve resulted in a loss of vibrissae-related cellular patterns in the brainstem, but TTX application and whisker clipping did not. These results raise the possibility that up-regulation of galanin and NPY may play a role in the disappearance of vibrissae-related cellular patterns in the brainstem of rats that sustain neonatal ION damage.

A transient projection from the trigeminal brainstem complex to the superficial layers of the hamster's superior colliculus

SummaryAnterograde tracing with the carbocyanine dye, Di-I, was used to describe the normal postnatal development of the projection from the trigeminal (V) brainstem complex to the superior colliculus (SC) in hamster. In adult hamsters, this projection is completely restricted to the deep laminae, primarily the stratum album intermedium. Trigeminal fibers were present in the SC by the day of birth, and at this time, they terminated mainly in the deep layers. However, labelled fibers also extended into the superficial laminae (the stratum griseum superficiale and stratum opticum) reaching as far as the SC surface. Trigeminal projections to the superficial SC laminae were visible as late as postnatal day (P-) 6, but were absent by P-8. During the period when V axons were present in the superficial SC laminae, they could not be detected in the dorsal lateral geniculate nucleus.

An endogenous peptide that induces long-term blood pressure elevation

A peptide was recently isolated from the blood of spontaneously hypertensive (SH) rats that stimulated an increase of calcium uptake by vascular tissue in vitro. In the present study normotensive rats were given nanomolar amounts of this peptide by intravenous or picomolar amounts by intracerebral injection and the effect on blood pressure was recorded. Injection of the peptide into the circulation had no significant effect on the elevation of blood pressure. By comparison, the injection of the compound into the third ventricle of the brain resulted in the elevation of blood pressure to hypertensive levels. The blood pressure response was characterized by a prolonged period of onset with maximal elevation observed several days after the beginning of treatment. Subsequently, the increase in blood pressure was well maintained with significant elevation noted days following the cessation of treatment.