Active dendritic currents gate descending cortical outputs in perception.

The output of cortical columns is routed to different downstream targets via distinct pathways: cortico-cortical and cortico-subcortical. It is as yet unclear what roles these pathways play in perception, and which cellular and circuit mechanisms regulate their gating. We recently showed that activation of the apical dendrites of layer 5 (L5) pyramidal neurons correlates with the threshold for perception, but these neurons come in two classes that target either other cortical or subcortical areas. In the present study, we took advantage of transgenic mouse lines for these L5 subclasses to determine their relative contributions to the perceptual process. We found that the activation of apical dendrites in neurons of the somatosensory cortex, which project to subcortical regions, almost exclusively determined the detection of tactile stimuli in mice. Our results suggest that dendritic activation drives context-dependent interactions between cortex and subcortical regions, including the higher-order thalamus, superior colliculus and striatum, which are crucial for perception.

Constant innervation despite pubertal growth of the mouse penis.

The sexual characteristics of the vertebrate body change under the control of sex hormones. In mammals, genitals undergo major changes in puberty. While such bodily changes have been well documented, the associated changes in the nervous system are poorly understood. To address this issue, we studied the growth and innervation of the mouse penis throughout puberty. To this end, we measured length and thickness of the mouse penis in prepubertal (3-4 week old) and adult (8-10 week old) mice and performed fiber counts of the dorsal penile nerve. We obtained such counts with confocal imaging of proximal sections of the mouse penis after paraffin embedding and antibody staining against Protein-Gene-Product-9.5 or Neurofilament-H in combination with antigen retrieval procedures. We find that the mouse penis grows roughly 1.4 times in both thickness and length. Fiber counts in the dorsal penile nerve were not different in prepubertal (1,620 ± 165 fibers per penis) and adult (1,572 ± 383 fibers per penis) mice, however. Antibody staining along with myelin staining by Luxol-Fast-Blue suggested about 57% of penile nerve fibers were myelinated. Quantification of the area of mouse somatosensory penis cortex allowed us to compare cortical magnification of the penile cortex and the whisker-barrel-cortex systems. This comparison suggested that 2 to 4 times less cortical area is devoted to a penile-nerve-fiber than to a whisker-nerve-fiber. The constant innervation of mouse penis through puberty suggests that the pubertal increase of cortical magnification of the penis is not simply a reflection of peripheral change.

Effects of Sexual Experience and Puberty on Mouse Genital Cortex revealed by Chronic Imaging.

The topographic map in layer 4 of somatosensory cortex is usually specified early postnatally and stable thereafter. Genital cortex, however, undergoes a sex-hormone- and sexual-touch-dependent pubertal expansion. Here, we image pubertal development of genital cortex in Scnn1a-Tg3-Cre mice, where transgene expression has been shown to be restricted to layer 4 neurons with primary sensory cortex identity. Interestingly, during puberty, the number of Scnn1a+ neurons roughly doubled within genital cortex. The increase of Scnn1a+ neurons was gradual and rapidly advanced by initial sexual experience. Neurons that gained Scnn1a expression comprised stellate and pyramidal neurons in layer 4. Unlike during neonatal development, pyramids did not retract their apical dendrites during puberty. Calcium imaging revealed stronger genital-touch responses in Scnn1a+ neurons in males versus females and a developmental increase in responsiveness in females. The first sexual interaction is a unique physical experience that often creates long-lasting memories. We suggest such experience uniquely alters somatosensory body maps.

Peeking into the sleeping brain: Using in vivo imaging in rodents to understand the relationship between sleep and cognition.

Sleep is well known to benefit cognitive function. In particular, sleep has been shown to enhance learning and memory in both humans and animals. While the underlying mechanisms are not fully understood, it has been suggested that brain activity during sleep modulates neuronal communication through synaptic plasticity. These insights were mostly gained using electrophysiology to monitor ongoing large scale and single cell activity. While these efforts were instrumental in the characterisation of important network and cellular activity during sleep, several aspects underlying cognition are beyond the reach of this technology. Neuronal circuit activity is dynamically regulated via the precise interaction of different neuronal and non-neuronal cell types and relies on subtle modifications of individual synapses. In contrast to established electrophysiological approaches, recent advances in imaging techniques, mainly applied in rodents, provide unprecedented access to these aspects of neuronal function in vivo. In this review, we describe various techniques currently available for in vivo brain imaging, from single synapse to large scale network activity. We discuss the advantages and limitations of these approaches in the context of sleep research and describe which particular aspects related to cognition lend themselves to this kind of investigation. Finally, we review the few studies that used in vivo imaging in rodents to investigate the sleeping brain and discuss how the results have already significantly contributed to a better understanding on the complex relation between sleep and plasticity across development and adulthood.

Publisher Correction: Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

In the originally published version of this Article, incorrect references were cited on two occasions in the Results section. Under the subheading 'Ca2+ activity in single dendrites and somata of L5 neurons', the final sentence of the second paragraph incorrectly cited reference 29 instead of reference 31. Under the subheading 'Spiking of L5 cell bodies is not influenced by spindles', the first sentence cited reference 30 instead of reference 29. These errors have now been corrected in both the PDF and HTML versions of the Article.

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

Development of rat female genital cortex and control of female puberty by sexual touch.

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

Polyploidy and the Cellular and Areal Diversity of Rat Cortical Layer 5 Pyramidal Neurons.

In many species, polyploidy, in which an increase in nuclear DNA content is accompanied by an increase in cell size, contributes to cellular diversity. In the rat visual cortex, most neurons are small and homogeneous in size, while layer 5 cells are heterogeneous, containing some very large neurons. To measure DNA content, we quantified nuclear chromocenters and integrated DNA/DAPI fluorescence. The results suggest that most cortical neurons, non-neuronal cells, parvalbumin-positive interneurons, and large entorhinal layer 2 stellate projection neurons are diploid. In contrast, chromocenter counts and integrated fluorescence are ∼2-fold higher for some excitatory neurons in layer 5, suggesting that large Ctip2-negative and Ctip2-positive layer 5 neurons might be tetraploid. The distribution of putatively tetraploid neurons differed between areas and showed sharp borders aligned with functional subdivisions of the somatosensory cortex. Telomere counting and flow cytometry supported layer 5 polyploidy. We conclude that polyploidy contributes to cellular and areal diversity of rat cortex.

Screening for depression in adolescents: validity of the patient health questionnaire in pediatric care.

BACKGROUND: This study examines the criterion validity of the Patient Health Questionnaire 9-item (PHQ-9) and 2-item (PHQ-2) version as a depression-screening instrument for adolescents. METHODS: Three hundred twenty-two adolescents aged 13-16 were recruited from pediatric hospitals. Criterion validity of the PHQ-9 and PHQ-2 was assessed against diagnoses of any depressive disorder provided by a structured diagnostic interview. Areas under the receiver operating characteristics curve (AUCs) and sensitivities and specificities at optimal cutoff points were computed for both versions of the PHQ. Besides the dimensional algorithm, a categorical algorithm was applied for the PHQ-9. Validity measures of both scoring procedures of the PHQ-9 as well as PHQ-2 were compared statistically. In addition, unaided clinical depression diagnoses by the attending pediatricians were evaluated. RESULTS: Using the dimensional algorithm, the AUCof the PHQ-9 (93.2%) was significantly higher than that of the PHQ-2 (87.2%). At optimal cutoffs, there was no significant difference in sensitivity (PHQ-9: 90.0%, PHQ-2: 85.0%), but in specificity (PHQ-9: 86.5%, PHQ-2: 79.4%). Although the categorical algorithm of the PHQ-9 was most specific (94.7%), sensitivity was just above chance (52.5%). The unaided clinical diagnoses yielded a sensitivity of 12.5% and a specificity of 96.0%. CONCLUSIONS: The dimensional algorithm of the PHQ-9 demonstrated high criterion validity, whereas the categorical algorithm should not be applied due to its low sensitivity. Even though the PHQ-2 performed well, validity of the PHQ-9 was still superior. Hence, the PHQ-9 can be recommended as depression screener for adolescents to improve recognition rates in pediatric care.

Depression in pediatric care: is the WHO-Five Well-Being Index a valid screening instrument for children and adolescents?

OBJECTIVE: This study investigated the criterion validity of the WHO-Five Well-Being Index (WHO-5) in screening for depression in pediatric care. METHOD: A total of 446 children aged 9 to 12 and 324 adolescents aged 13 to 16, recruited from pediatric hospitals, completed the WHO-5 and a structured diagnostic interview serving as the gold standard. Diagnoses of depressive disorder included major depression and minor depression. Criterion validity was analyzed using the area under the receiver operating curve (AUC). Sensitivity and specificity were computed for optimal cutoffs. Additionally, unaided clinical diagnoses of depression made by the attending pediatricians were assessed. RESULTS: Diagnoses of depressive disorder were established for 3.6% of children and 11.7% of adolescents. AUCs were .88 for the child and .87 for the adolescent sample. A cutoff score of 10 for children maximized sensitivity (.75) and specificity (.92). For the adolescent sample, decreasing the cutoff score to 9 yielded optimal sensitivity (.74) and specificity (.89). Sensitivity of the unaided clinical diagnosis of depression was .09, while specificity was .96. CONCLUSIONS: The WHO-5 demonstrated good diagnostic accuracy for both age groups. Further evidence is needed to support the feasibility of the WHO-5 as a depression screening instrument used in pediatric care.