penectomy, urethroplasty and labiaplasty, 207 (93%) had formation of a neoclitoris, and 202 (91%) had a skin-lined neovagina. The median (range) age was 41 (19-76) years. The median hospital stay was 10 (6-21) days. A record of the first outpatient visit was available in 197 (84.5%) cases. The median time to follow up was 56 (8-351) days. Over all, 82.2% had an adequate vaginal depth, with a median depth of 13 (5-15) cm and 6.1% had developed vaginal stenosis. Three (1.7%) patients had had a vaginal prolapse, two (1.1%) had a degree of vaginal skin flap necrosis and one (0.6%) was troubled with vaginal hair growth. In 86.3% of the patients the neoclitorizes were sensitive. There was urethral stenosis in 18.3% of the patients and 5.6% complained of spraying of urine. Minor corrective urethral surgery was undertaken in 36 patients including 42 urethral dilatations, and eight meatotomies were performed. At the first clinic visit 174 (88.3%) patients were 'happy', 13 (6.6%) were 'unhappy' and 10 (5.1%) made no comment. Of the 233 patients, we successfully contacted 70 (30%). All had had penectomy and labioplasty, 64 (91%) had a clitoroplasty and 62 (89%) a neovagina. The median age was 43 (19-76) years and the median follow up was 36 (9-96) months. Overall, 63 (98%) had a sensate neoclitoris, with 31 (48%) able to achieve orgasm; nine (14%) were hypersensitive. Vaginal depth was considered adequate by 38 (61%) and 14 (23%) had or were having regular intercourse. Vaginal hair growth troubled 18 (29%), four (6%) had a vaginal prolapse and two (3%) had vaginal necrosis. Urinary problems were reported by 19 (27%) patients, of these 18 (26%) required revision surgery, 14 (20%) complained of urinary spraying, 18 (26%) had an upward directed stream and 16 (23%) had urethral stenosis. The patients deemed the cosmetic result acceptable in 53 (76%) cases and 56 (80%) said the surgery met with their expectations. CONCLUSIONThis is largest series of early results after male to female FG. Complications are common after this complex surgery and long-term follow-up is difficult, as patients tend to relocate at the start of their 'new life' after FG. There were good overall cosmetic and functional results, with a sustained high patient satisfaction. KEYWORDS OBJECTIVETo examine the early and late surgical outcomes of feminizing genitoplasty (FG) in adult transsexuals in a UK single surgeon practice over a 10-year period. PATIENTS AND METHODSComputerized and manual databases were searched over the period 1994-2004 to identify patients who had undergone male to female FG. Case-notes were retrieved and analysed to identify epidemiological data, the number and type of perioperative problems, early results at outpatient review, late occurring problems and patient satisfaction. A telephone questionnaire was then conducted targeting all FG patients in our series. The questions were directed at identifying surgical complications, outcome and patient satisfaction. RESULTSIn all, 233 case-notes were identified and 222 (95%) were retrieved....

1. The synaptic linkage between single, identified slowly adapting type I (SAI) fibres and their central target neurones of the cuneate nucleus was examined in pentobarbitoneanaesthetized cats. Simultaneous extracellular recordings were made from individual cuneate neurones and from fine, intact fascicles of the lateral branch of the superficial radial nerve in which it was possible to identify and monitor the activity of each group II fibre. Individual SAI fibres were activated by static displacement and by vibration delivered with a fine probe (0-25-2 mm diameter) to their associated touch domes in the hairy skin of the forelimb. 2. Transmission properties across the synapse were analysed for nine SAI-cuneate pairs in which the single SAI fibre of each pair provided a suprathreshold input to the cuneate neurone. Neither spatial nor temporal summation was required for effective impulse transmission, and often more than 80 % of SAI impulses led to a response in the cuneate neurone. Responses of the cuneate neurones to single SAI impulses occurred at a short, fixed latency (S.D. often < 0 1 ms), and frequently consisted of a burst of two or three impulses, at low SAI input rates in particular. 3. The tight phase-locking in the responses to vibration of single SAI fibres was preserved in the cuneate responses for frequencies up to -400 Hz. However, as the impulse rates of the cuneate neurones were less than 150 impulses s', their impulse patterns could not

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organized by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organization and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organization, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibers, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organization and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

The prelimbic region of medial frontal cortex in the rat receives a direct input from the hippocampus and this functional connection is essential for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated slices of frontal cortex. Repetitive bursts of stimulation at theta frequencies (TBS) were applied to layer II, and monosynaptic EPSPs were monitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimulation at 100 Hz in the presence of the N-methyl--aspartate (NMDA)-antagonist 2-amino-5-phosphonopentanoate (AP5) was reported to be a reliable method of inducing LTD in prelimbic cortex (). However we found that this protocol did not facilitate the induction of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R, S)-alpha-methyl-4- carboxyphenylglycine (MCPG). This drug significantly reduced the incidence of LTP after TBS to only 1 of 14 neurons (P < 0.02, chi2 test). The pooled responses to TBS in MCPG showed significantly reduced potentiation [(P < 0.02, analysis of variance (ANOVA)]. The broad-spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylglycine(S-3HPG) both produced membrane depolarization, an increase in number of spikes evoked by depolarizing current pulses, and a reduction in the afterhyperpolarization. Similar effects were produced by these agonists even when synaptic transmission was blocked by use of the gamma-aminobutyric acid-B (GABAB) receptor agonist, 200 microM baclofen, which suggests that group I mGluRs are present on layer V neurons. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and that this excitatory effect could be mediated by the postsynaptic group I mGluRs.

Skin vibrations sensed by tactile receptors contribute significantly to the perception of object properties during tactile exploration [1-4] and to sensorimotor control during object manipulation [5]. Sustained low-frequency skin vibration (<60 Hz) evokes a distinct tactile sensation referred to as flutter whose frequency can be clearly perceived [6]. How afferent spiking activity translates into the perception of frequency is still unknown. Measures based on mean spike rates of neurons in the primary somatosensory cortex are sufficient to explain performance in some frequency discrimination tasks [7-11]; however, there is emerging evidence that stimuli can be distinguished based also on temporal features of neural activity [12, 13]. Our study's advance is to demonstrate that temporal features are fundamental for vibrotactile frequency perception. Pulsatile mechanical stimuli were used to elicit specified temporal spike train patterns in tactile afferents, and subsequently psychophysical methods were employed to characterize human frequency perception. Remarkably, the most salient temporal feature determining vibrotactile frequency was not the underlying periodicity but, rather, the duration of the silent gap between successive bursts of neural activity. This burst gap code for frequency represents a previously unknown form of neural coding in the tactile sensory system, which parallels auditory pitch perception mechanisms based on purely temporal information where longer inter-pulse intervals receive higher perceptual weights than short intervals [14]. Our study also demonstrates that human perception of stimuli can be determined exclusively by temporal features of spike trains independent of the mean spike rate and without contribution from population response factors.

The brainstem dorsal column nuclei (DCN) are essential to inform the brain of tactile and proprioceptive events experienced by the body. However, little is known about how ascending somatosensory information is represented in the DCN. Our objective was to investigate the usefulness of high-frequency (HF) and low-frequency (LF) DCN signal features (SFs) in predicting the nerve from which signals were evoked. We also aimed to explore the robustness of DCN SFs and map their relative information content across the brainstem surface. DCN surface potentials were recorded from urethane-anesthetized Wistar rats during sural and peroneal nerve electrical stimulation. Five salient SFs were extracted from each recording electrode of a seven-electrode array. We used a machine learning approach to quantify and rank information content contained within DCN surface-potential signals following peripheral nerve activation. Machine-learning of SF and electrode position combinations was quantified to determine a hierarchy of information importance for resolving the peripheral origin of nerve activation. A supervised back-propagation artificial neural network (ANN) could predict the nerve from which a response was evoked with up to 96.8 ± 0.8% accuracy. Guided by feature-learnability , we maintained high prediction accuracy after reducing ANN algorithm inputs from 35 (5 SFs from 7 electrodes) to 6 (4 SFs from one electrode and 2 SFs from a second electrode). When the number of input features were reduced, the best performing input combinations included HF and LF features. Feature-learnability also revealed that signals recorded from the same midline electrode can be accurately classified when evoked from bilateral nerve pairs, suggesting DCN surface activity asymmetry. Here we demonstrate a novel method for mapping the information content of signal patterns across the DCN surface and show that DCN SFs are robust across a population. Finally, we also show that the DCN is functionally asymmetrically organized, which challenges our current understanding of somatotopic symmetry across the midline at sub-cortical levels.

Transmission from single, identified, slowly adapting type II (SAII) tactile fibers to their target neurons in the cuneate nucleus was examined in anesthetized cats. Simultaneous recordings were made from cuneate neurons and from fine, intact fascicles of the superficial radial nerve in which it was possible to identify and monitor the activity of each group II fiber. Selective activation of individual SAII fibers was achieved by means of skin stimulation with fine probes, in conjunction with extensive forelimb denervation. Responses were studied for seven SAII-driven cuneate neurons. For three there was unequivocal monitoring of the identified SAII input fiber. However, in six of the seven there was evidence that just one SAII fiber provided suprathreshold input to the cuneate neuron, and neither temporal nor spatial summation was required for reliable transmission. Cuneate impulse rates, in response to SAII inputs lasting 1 s, were less than 250 impulses per second, even though the SAII impulse rates could be 500 s-1. Responses to individual SAII impulses consisted of a burst of 2-3 impulses at low SAII input rates, but burst responses disappeared at high SAII rates. In all three SAII-cuneate pairs studied, the transmission security (the percentage of SAII impulses that evoked cuneate spike output) exceeded 80% in response to static skin displacement and in response to certain frequencies of skin vibration, in particular, at 100-200 Hz, exceeded 98% when the SAII fiber responded near the 1:1 level (one impulse per vibration cycle).(ABSTRACT TRUNCATED AT 250 WORDS)

The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies < 60 Hz) and vibratory hum (frequencies > 60 Hz), subserved by two distinct receptor types (Meissner’s and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types.