Two types of vibrissal surface structures, undulated and smooth, exist among pinnipeds. Most Phocidae have vibrissae with undulated surfaces, while Otariidae, Odobenidae, and a few phocid species possess vibrissae with smooth surfaces. Variations in cross-sectional profile and orientation of the vibrissae also exist between pinniped species. These factors may influence the way that the vibrissae behave when exposed to water flow. This study investigated the effect that vibrissal surface structure and orientation have on flow-induced vibrations of pinniped vibrissae. Laser vibrometry was used to record vibrations along the whisker shaft from the undulated vibrissae of harbor seals (Phoca vitulina) and northern elephant seals (Mirounga angustirostris) and the smooth vibrissae of California sea lions (Zalophus californianus). Vibrations along the whisker shaft were measured in a flume tank, at three orientations (0°, 45°, 90°) to the water flow. The results show that vibration frequency and velocity ranges were similar for both undulated and smooth vibrissae. Angle of orientation, rather than surface structure, had the greatest effect on flow-induced vibrations. Vibration velocity was up to 60 times higher when the wide, flat aspect of the whisker faced into the flow (90°), compared to when the thin edge faced into the flow (0°). Vibration frequency was also dependent on angle of orientation. Peak frequencies were measured up to 270 Hz and were highest at the 0° orientation for all whiskers. Furthermore, CT scanning was used to quantify the three-dimensional structure of pinniped vibrissae that may influence flow interactions. The CT data provide evidence that all vibrissae are flattened in cross-section to some extent and that differences exist in the orientation of this profile with respect to the major curvature of the hair shaft. These data support the hypothesis that a compressed cross-sectional profile may play a key role in reducing self-noise of the vibrissae.

The development, maintenance and regeneration of epithelial appendages such as hairs or vibrissae depend on reciprocal interactions between the epidermal and the dermal components of the integument. Growth factors are among a number of signaling molecules that have been identified during these developmental events. Growth factors such as fibroblast growth factors (FGFs) bind cell surface heparan sulfate proteoglycans (HSPGs) on their heparan sulfate side chains and as such these proteoglycans act as co-receptors for FGF receptors (FGFRs) by forming a ternary signaling complex of HSPG, FGFR and FGF. The syndecans make up a family (syndecan-1-4) of transmembrane HSPGs. In the present study we examined the growth response of mouse vibrissae to HSPG-binding growth factors as a function of the presence or absence of syndecan-4 in an organ culture system. Syndecan-4 is expressed on keratinocytes that make up the inner root sheath of the vibrissa. Vibrissae from wild-type mice, but not from syndecan-4 null mice, displayed a statistically significant and dose-dependent growth response to FGF-1, FGF-2 and FGF-7. In contrast, a statistically significant growth response is seen in vibrissae from both wild-type and syndecan-4 null mice when the culture medium is supplemented with either hepatocyte growth factor (HGF) that binds to HSPG, insulin that does not bind to HSPG or 5% fetal bovine serum. The syndecan-4 dependent effect of FGF-1, -2 and -7 on the transcriptional activity of IRS expressed genes and of genes involved in cell proliferation reveals a number of different response patterns. In vivo, the vibrissae of syndecan-4 null mice are shorter and have a smaller diameter than those of wild-type mice and this phenotype may result from a suboptimal response to growth factors. Syndecan-1, which is expressed in the outer root sheath of the vibrissae shaft, does not influence the response of the vibrissae to FGF-1, -2 and -7 and the length and diameter of vibrissae of syndecan-1 null mice do not differ from those of wild-type mice.

During natural exploration, rats exhibit two particularly conspicuous vibrissal-mediated behaviors: they follow along walls, and "dab" their snouts on the ground at frequencies related to the whisking cycle. In general, the walls and ground may be located at any distance from, and at any orientation relative to, the rat's head, which raises the question of how the rat might determine the position and orientation of these surfaces. Previous studies have compellingly demonstrated that rats can accurately determine the horizontal angle at which a vibrissa first touches an object, and we therefore asked whether this parameter could provide the rat with information about the pitch, distance, and yaw of a surface relative to its head. We used a three-dimensional model of the whisker array to construct mappings between the horizontal angle of contact of each vibrissa and every possible (pitch, distance, and yaw) configuration of the head relative to a flat surface. The mappings revealed striking differences in the patterns of contact for vibrissae in different regions of the array. The exterior (A, D, E) rows provide information about the relative pitch of the surface regardless of distance. The interior (B, C) rows provide distance cues regardless of head pitch. Yaw is linearly correlated with the difference between the number of right and left whiskers touching the surface. Compared to the long reaches that whiskers can make to the side and below the rat, the reachable distance in front of the rat's nose is relatively small. We confirmed key predictions of these functional groupings in a behavioral experiment that monitored the contact patterns that the vibrissae made with a flat vertical surface. These results suggest that vibrissae in different regions of the array are not interchangeable sensors, but rather functionally grouped to acquire particular types of information about the environment.

Hair follicle stem cells (HFSCs) possess fascinating self-renewal capacity and multipotency, which play important roles in mammalian hair growth and skin wound repair. Although HFSCs from other mammalian species have been obtained, the characteristics of ovine HFSCs, as well as the methods to isolate them have not been well addressed. Here, we report an efficient strategy to obtain multipotent ovine HFSCs. Through microdissection and organ culture, we obtained keratinocytes that grew from the bulge area of vibrissa hair follicles, and even abundant keratinocytes were harvested from a single hair follicle. These bulge-derived keratinocytes are highly positive for Krt15, Krt14, Tp63, Krt19 and Itga6; in addition to their strong proliferation abilities in vitro, these keratinocytes formed new epidermis, hair follicles and sebaceous glands in skin reconstitution experiments, showing that these are HFSCs from the bulge outer root sheath. Taken together, we developed an efficient in vitro system to enrich ovine HFSCs, providing enough HFSCs for the investigations about the ovine hair cycle, aiming to promote wool production in the future.

The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with classical conditioning procedures. Nonetheless, it is not known yet which brain structures, or neuronal mechanisms, are responsible for the acquisition, storage, and expression of these motor responses. Here, we studied the temporal correlation between unitary activities of identified eyelid and vibrissae motor cortex neurons and the electromyographic activity of the orbicularis oculi and vibrissae muscles and magnetically recorded eyelid positions during classical conditioning of eyelid and vibrissae responses, using both delay and trace conditioning paradigms in behaving mice. We also studied the involvement of motor cortex neurons in reflexively evoked eyelid responses and the kinematics and oscillatory properties of eyelid movements evoked by motor cortex microstimulation. Results show the involvement of the motor cortex in the performance of conditioned responses elicited during the classical conditioning task. However, a timing correlation analysis showed that both electromyographic activities preceded the firing of motor cortex neurons, which must therefore be related more with the reinforcement and/or proper performance of the conditioned responses than with their acquisition and storage.

Hypertrichosis is one of the most common side effects of systemic cyclosporine A therapy. It has been previously shown that cyclosporine A induces anagen and inhibits catagen development in mice. In the present study, to explore the mechanisms of cyclosporine A, we investigated the effects of cyclosporine A on hair shaft elongation, hair follicle cell proliferation, apoptosis, and mRNA expression of selected growth factors using an organ culture model of mouse vibrissae. In this model, cyclosporine A stimulated hair growth of normal mouse vibrissae follicles by inhibiting catagen-like development and promoting matrix cell proliferation. In addition, cyclosporine A caused an increase in the expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and nerve growth factor (NGF), and inhibited follistatin expression. Our findings provide an explanation for the clinically observed effects of cyclosporine A on hair growth. The mouse vibrissae organ culture offers an attractive model for identifying factors involved in the modulation of hair growth.

The morphology of an animal's face will have large effects on the sensory information it can acquire. Here we quantify the arrangement of cranial sensory structures of the rat, with special emphasis on the mystacial vibrissae (whiskers). Nearly all mammals have vibrissae, which are generally arranged in rows and columns across the face. The vibrissae serve a wide variety of important behavioral functions, including navigation, climbing, wake following, anemotaxis, and social interactions. To date, however, there are few studies that compare the morphology of vibrissal arrays across species, or that describe the arrangement of the vibrissae relative to other facial sensory structures. The few studies that do exist have exploited the whiskers' grid-like arrangement to quantify array morphology in terms of row and column identity. However, relying on whisker identity poses a challenge for comparative research because different species have different numbers and arrangements of whiskers. The present work introduces an approach to quantify vibrissal array morphology regardless of the number of rows and columns, and to quantify the array's location relative to other sensory structures. We use the three-dimensional locations of the whisker basepoints as fundamental parameters to generate equations describing the length, curvature, and orientation of each whisker. Results show that in the rat, whisker length varies exponentially across the array, and that a hard limit on intrinsic curvature constrains the whisker height-to-length ratio. Whiskers are oriented to "fan out" approximately equally in dorsal-ventral and rostral-caudal directions. Quantifying positions of the other sensory structures relative to the whisker basepoints shows remarkable alignment to the somatosensory cortical homunculus, an alignment that would not occur for other choices of coordinate systems (e.g., centered on the midpoint of the eyes). We anticipate that the quantification of facial sensory structures, including the vibrissae, will ultimately enable cross-species comparisons of multi-modal sensing volumes.

The tish rat is a neurological mutant exhibiting bilateral cortical heterotopia similar to those found in certain epileptic patients. Previous work has shown that thalamocortical fibers originating in the ventroposteromedial nucleus, which in normal animals segregate as 'barrel' representations for individual whiskers, terminate in both normotopic and heterotopic areas of the tish cortex (Schottler et al., 1998). Thalamocortical innervation terminates as barrels in layer IV and diffusely in layer VI of the normotopic area. Discrete patches of terminals are also observed in the underlying heterotopic area suggesting that representations of individual vibrissa may be present in the heterotopic somatosensory areas. The present study examines this issue by investigating the organization of the vibrissal somatosensory system in the tish cortex. Staining for cytochrome oxidase or Nissl substance reveals a normal complement of vibrissal barrels in the normotopic area of the tish cortex. Dense patches of cytochrome oxidase staining are also found in the underlying lateral portions of the heterotopic area (i.e. the same area that is innervated by the ventroposteromedial nucleus). Injections of retrograde tracers into vibrissal areas of either the normotopic or heterotopic area produce topographically organized labeling of neurons restricted to one or a small number of barreloids within the ventroposteromedial nucleus of the thalamus. Physical stimulation of a single whisker (D3 or E3) elicits enhanced uptake of [(14)C]2-deoxyglucose in restricted zones of both the normotopic and heterotopic areas, demonstrating that single whisker stimulation can increase functional activity in both normotopic and heterotopic neurons. These findings indicate that the barrels are intact in the normotopic area and are most consistent with the hypothesis that at least some of the individual vibrissae are 'dually' represented in normotopic and heterotopic positions in the primary somatosensory areas of the tish cortex.

The terminal Schwann cells that accompany lanceolate sensory endings in the rat vibrissal follicle are known to display the small plasma membrane invaginations termed caveolae, which concentrate Ca(2+) signaling molecules. We have previously shown that these cells generate Ca(2+) signals at the lamellar processes covering the receptor axons through activation of the metabotropic purinoceptor P2Y(2). To investigate the roles of caveolae in the spatiotemporal organization of Ca(2+) signals, terminal Schwann cells were observed by immunohistochemistry for the caveola protein caveolin-1, and by transmission and scanning electron microscopy. In addition, immunohistochemical detection of P2Y(2) and its coupling partner G(q/11) along with confocal image analysis of the purinergically induced glial Ca(2+) responses was performed in isolated tissue preparations either treated or untreated with the caveolae eliminator methyl-β-cyclodextrin. Results showed the Schwann lamellae to be characterized by the presence of dense caveolae accompanying a fine tubular network of the endoplasmic reticulum Ca(2+) store and by intense expression of the signaling molecules P2Y(2) and G(q/11). Loss of caveolae diffusely redistributed these molecules throughout the entire cell and impaired the lamellar Ca(2+) signals, both in chronological priority (preceding the global cell response) and in spatial integrity (involving the entire length of the processes). To our knowledge, this is the first report of a subcellular accumulation of caveolae underlying compartmentalized glial Ca(2+) signals that can couple with local effects on the accompanying axon terminals.

Manipulation of cortical serotonin (5-HT) levels in perinatal rodents produces significant alterations in the development of the layer IV cortical representation of the mystacial vibrissae. Monoamine oxidase A (MAO(A)) knockout mice have highly elevated cortical 5-HT and completely lack barrels in somatosensory cortex (S-I). The present study was undertaken to determine whether the effects on thalamocortical development seen in MAO(A) knockout mice can be replicated in perinatal rats treated with an MAO(A) inhibitor and, second, to determine whether these effects persist with continued treatment or after discontinuation of the drug. Littermates were injected with either clorgyline (5 mg/kg) or sterile saline five times daily. Clorgyline administration from birth to postnatal day (P) 6, 8, or 10 produced increases of 1,589.4 +/- 53.3%, 1660.2 +/- 43.1% and 1,700.5 +/- 84.5 %, respectively, in cortical 5-HT as compared with controls. Serotonin immunocytochemistry, 1,1;-dioctadecyl-3,3,3", 3;-tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamocortical afferents and Nissl and cytochrome oxidase staining of layer IV cellular aggregates demonstrated that clorgyline treatment from P0 to P6 produced a complete absence of any segmentation of vibrissae-related patches in S-I. However, continued treatment until P8 or P10 did not prevent the appearance of these patches. Animals treated with clorgyline from birth to P6 and killed on P8 or P10 had increases of 546.8 +/- 33.2% and 268.8 +/- 6.3% in cortical 5-HT and they had qualitatively normal vibrissae-related patterns in S-I. These results indicate that clorgyline treatment produces a transient disruption of vibrissae-related patterns, despite the continued presence of elevated cortical 5-HT.

To investigate the growth potential of keratinocytes derived from the germinative epithelium (GE) of ovine hair follicles. Stem cells from the outer root sheath (ORS) of hair follicles migrate to the GE in the lower follicle where they proliferate and differentiate to form the hair fiber. It has been suggested that the GE comprises transit-amplifying cells and that the duration of anagen is determined by their limited proliferative potential. However, we show here that keratinocytes derived from the GE of ovine follicles grow extensively in vitro, arguing against this hypothesis.

Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To investigate the effect of Activin B on vibrissae follicles, the anagen induction assay and an in vitro vibrissae culture system were constructed. Hematoxylin and eosin staining were performed to determine the hair cycle stages. The 5-ethynyl-2'-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays were used to examine the cell proliferation. Flow cytometry was used to detect the cell cycle phase. Inhibitors and Western blot analysis were used to investigate the signaling pathway induced by Activin B. As a result, we found that the vibrissae follicle growth was accelerated by 10 ng/mL Activin B in the anagen induction assay and in an organ culture model. 10 ng/mL Activin B promoted hair matrix cell proliferation in vivo and in vitro. Moreover, Activin B modulates hair matrix cell growth through the ERK⁻Elk1 signaling pathway, and Activin B accelerates hair matrix cell transition from the G1/G0 phase to the S phase through the ERK⁻Cyclin D1 signaling pathway. Taken together, these results demonstrated that Activin B may promote mouse vibrissae growth by stimulating hair matrix cell proliferation and cell cycle progression through ERK signaling.

To search hair growth-promoting herbal extract, a screening platform of having HEK293T fibroblast being transfected with pTOPFLASH DNA construct was developed over a thousand of herbal extracts and phytochemicals were screened. One of the hits was ethanolic extract of Rhizoma Belamcandae, the rhizome of Belamcanda chinensis (L.) DC. Tectoridin, an isoflavone from Rhizoma Belamcandae, was shown to be responsible for this activation of promoter construct, inducing the transcription of pTOPFLASH in the transfected fibroblasts in a dose-dependent manner. The blockage by DKK-1 suggested the action of tectoridin could be mediated by the Wnt receptor. The hair growth-promoting effects of tectoridin were illustrated in human follicular dermal papilla cells and mouse vibrissae organ cultures. In tectoridin-treated dermal papilla cultures, an activation of Wnt signaling was demonstrated by various indicative markers, including TCF/LEF1 transcriptional activity, nuclear translocation of β-catenin, expressions level of mRNAs encoding axin-related protein, (AXIN2), β-catenin, lymphoid enhancer-binding factor-1 (LEF-1), insulin-like growth factor 1 (IGF-1) and alkaline phosphatase (ALP). In addition, an increase of hair shaft elongation was observed in cultured mouse vibrissae upon the treatment of tectoridin. Tectoridin, as well as the herbal extract of Rhizoma Belamcandae, possesses hair promoting activity, which deserves further development.

TONIC (SLOWLY ADAPTING) AND PHASIC (RAPIDLY ADAPTING) PRIMARY AFFERENTS CONVEY COMPLEMENTARY ASPECTS OF HAPTIC INFORMATION TO THE CENTRAL NERVOUS SYSTEM: object location and texture the former, shape the latter. Tonic and phasic neural responses are also recorded in all relay stations of the somatosensory pathway, yet it is unknown their role in both, information processing and information transmission to the cortex: we don't know if tonic and phasic neurons process complementary aspects of haptic information and/or if these two types constitute two separate channels that convey complementary aspects of tactile information to the cortex. Here we propose to elucidate these two questions in the fast trigeminal pathway of the rat (PrV-VPM: principal trigeminal nucleus-ventroposteromedial thalamic nucleus). We analyze early and global behavior, latencies and stability of the responses of individual cells in PrV and medial lemniscus under 1-40 Hz stimulation of the whiskers in control and decorticated animals and we use stochastic spiking models and extensive simulations. Our results strongly suggest that in the first relay station of the somatosensory system (PrV): (1) tonic and phasic neurons process complementary aspects of whisker-related tactile information (2) tonic and phasic responses are not originated from two different types of neurons (3) the two responses are generated by the differential action of the somatosensory cortex on a unique type of PrV cell (4) tonic and phasic neurons do not belong to two different channels for the transmission of tactile information to the thalamus (5) trigeminothalamic transmission is exclusively performed by tonically firing neurons and (6) all aspects of haptic information are coded into low-pass, band-pass, and high-pass filtering profiles of tonically firing neurons. Our results are important for both, basic research on neural circuits and information processing, and development of sensory neuroprostheses.

Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen the association between the presence of the penile spine/vibrissa enhancer and the presence of penile spines and macro- or micro- vibrissae in non-human primates as well as show that loss of the enhancer is both a distinctive and characteristic feature of the human lineage.

The array of vibrissae on a rat's face is the first stage in a high-resolution tactile sensing system. Progressing from rostral to caudal in any vibrissae row results in an increase in whisker length and thickness. This may, in turn, provide a systematic map of separate tactile channels governed by the mechanical properties of the whiskers. To examine whether this map is expressed in a location-dependent transformation of tactile signals into whisker vibrations and neuronal responses, we monitored whiskers' movements across various surfaces and edges. We found a robust rostral-caudal (R-C) gradient of tactile information transmission in which rostral shorter vibrissae displayed a higher sensitivity and bigger differences in response to different textures, whereas longer caudal vibrissae were less sensitive. This gradient is evident in several dynamic properties of vibrissae trajectories. As rodents sample the environment with multiple vibrissae, we found that combining tactile signals from multiple vibrissae resulted in an increased sensitivity and bigger differences in response to the different textures. Nonetheless, we found that texture identity is not represented spatially across the whisker pad. Based on the responses of first-order sensory neurons, we found that they adhere to the tactile information conveyed by the vibrissae. That is, neurons innervating rostral vibrissae were better suited for texture discrimination, whereas neurons innervating caudal vibrissae were more suited for edge detection. These results suggest that the whisker array in rodents forms a sensory structure in which different facets of tactile information are transmitted through location-dependent gradient of vibrissae on the rat's face.

In nature, there are several examples of sophisticated sensory systems to sense flows, e.g., the vibrissae of mammals. Seals can detect the flow of their prey, and rats are able to perceive the flow of surrounding air. The vibrissae are arranged around muzzle of an animal. A vibrissa consists of two major components: a shaft (infector) and a follicle-sinus complex (receptor), whereby the base of the shaft is supported by the follicle-sinus complex. The vibrissa shaft collects and transmits stimuli, e.g., flows, while the follicle-sinus complex transduces them for further processing. Beside detecting flows, the animals can also recognize the size of an object or determine the surface texture. Here, the combination of these functionalities in a single sensory system serves as paragon for artificial tactile sensors. The detection of flows becomes important regarding the measurement of flow characteristics, e.g., velocity, as well as the influence of the sensor during the scanning of objects. These aspects are closely related to each other, but, how can the characteristics of flow be represented by the signals at the base of a vibrissa shaft or by an artificial vibrissa-like sensor respectively? In this work, the structure of a natural vibrissa shaft is simplified to a slender, cylindrical/tapered elastic beam. The model is analyzed in simulation and experiment in order to identify the necessary observables to evaluate flows based on the quasi-static large deflection of the sensor shaft inside a steady, non-uniform, laminar, in-compressible flow.

Somatosensation is the primary sensory modality employed by rodents in navigating their environments, and mystacial vibrissae on the snout are the primary conveyors of this information to the murine brain. The layout of vibrissae is spatially stereotyped and topographic connections faithfully maintain this layout throughout the neuraxis. Several factors have been shown to influence general vibrissal innervation by trigeminal neurons. Here, the role of a cell surface receptor, EphA4, in directing position-dependent vibrissal innervation is examined. EphA4 is expressed in the ventral region of the presumptive whisker pad and EphA4(-/-) mice lack the ventroposterior-most vibrissae. Analyses reveal that ventral trigeminal axons are abnormal, failing to innervate emerging vibrissae, and resulting in the absence of a select group of vibrissae in EphA4(-/-) mice. EphA4's selective effect on a subset of whiskers implicates cell-based signaling in the establishment of position-dependent connectivity and topography in the peripheral somatosensory system.

Gray seals (Halichoerus grypus) have been rapidly recolonizing the Northeast US coast, eliciting concern from the fishing industry. However, the ecological effect of this recovery is still unknown and as such, research is needed to better understand how the diet composition of gray seals in US waters will contribute to the ecological impact. While previous research on seal diets has focused on the analysis of hard prey remains, stable isotope analysis presents an alternative method that can be used to describe marine mammal diets when direct observation is impossible. To address this issue, we used stable isotope analysis of gray seal pup vibrissae and lanugo from Monomoy Island, Cape Cod, MA during the 2015/2016 winter breeding season to estimate adult female diet composition during pregnancy. Stable isotope mixing models (SIMM) suggested adult female gray seals were consuming greater amounts of cephalopod prey and less sand lance than previously indicated from analysis of hard prey remains. However, using SIMMs to estimate the diet composition of gray seals remains difficult due to the large number of isotopically similar prey species and uncertainty in tissue-specific, stable isotope trophic enrichment factors. Even so, by combining prey sources into ecologically informative groups and integrating prior information into SIMMs it is possible to obtain additional insights into the diet of this generalist predator.

Elevating cortical serotonin (5-HT) in rats with clorgyline, a monoamine oxidase A (MAO(A)) inhibitor, from postnatal day (P-0) to P-6 delays the organization of thalamocortical afferent fibers into a vibrissae-related pattern in the somatosensory cortex (S-I). Despite continued elevation of cortical 5-HT through P-8, the thalamocortical fibers do form, albeit with some delay, a characteristic vibrissae pattern of barrels in layer IV of S-I by P-8. The growth-associated protein, GAP-43, is transiently expressed in developing S-I cortex of normal rats in a vibrissae related pattern until P-7. After P-7, GAP-43 expression is reduced in the barrel centers and increased in the septa. The present study evaluated the effect of elevated 5-HT levels on the distribution of GAP-43 immunoreactivity in S-I. We employed 5-HT immunocytochemistry and 1,1'-dioctadecyl-3,3,3",3'-tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamic radiations to confirm a 'barrelless' phenotype in P-6 clorgyline-treated animals and a recovered barrel pattern in treated animals allowed to survive until P-8 and P-10. GAP-43 immunocytochemistry was used to evaluate the cortical distribution of this protein in similarly treated littermates. Continuous inhibition of MAO(A) from P-0 to P-6 resulted in a corresponding loss of the GAP-43 vibrissae-related pattern at P-6. Despite continued elevation of cortical 5-HT until P-8 and P-10, the characteristic vibrissae-complementary pattern of GAP-43 emerged with expression concentrated in the septa and rows. GAP-43 vibrissae-related thalamocortical axon pattern never appeared in the clorgyline-treated animals. Thus, while elevated 5-HT delays development of a vibrissae-related pattern of thalamocortical afferents, it does not appear to alter the time when a GAP-43 vibrissae-related complementary pattern emerges.