In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise during cortical development. We therefore asked whether postsynaptic BDNF signaling through its receptor TrkB regulates spine persistence in adult V1. This question has been difficult to address because most methods used to alter TrkB signaling in vivo affect cortical development or cannot distinguish between pre-and postsynaptic mechanisms. We circumvented these problems by employing transgenic mice expressing a dominant negative TrkB-EGFP fusion protein in sparse pyramidal neurons of the adult neocortex and hippocampus, producing a Golgi-staining-like pattern. In adult V1, expression of dominant negative TrkB-EGFP resulted in reduced mushroom spine maintenance and synaptic efficacy, accompanied by an increase in long and thin spines and filopodia. In contrast, mushroom spine maintenance was unaffected in CA1, indicating that TrkB plays fundamentally different roles in structural plasticity in these brain areas.adult cortical plasticity ͉ BDNF signaling ͉ synapse stability ͉ transgenic mice D uring development, synapse formation and elimination are regulated by molecular cues, spontaneous activity, and experience (1, 2). Most glutamatergic synapses on excitatory neurons are situated on dendritic spines. Live imaging of neurons expressing GFP has provided important information on the dynamics of spine formation and maintenance (3-8). Filopodia are short-lived fingershaped protrusions and believed to be precursors of dendritic spines (9, 10). Newly formed spines are often thin or long and appear and disappear within days. Some mature into mushroom or stubby spines, which are more stable and often persist for months (7,8). There are strong correlations between spine size, spine persistence, synaptic efficacy, and the number of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) at the postsynaptic density (8,11,12). With development and aging of the cortex, there is a shift toward larger and more persistent spine types (3,7,13).Spine dynamics are influenced by plasticity. Long-term potentiation in hippocampus is associated with an increase in spine size (14) and spine formation (15), whereas term depression is associated with spine elimination (16). Interestingly, reducing synaptic input results in an increase in spine numbers, probably due to homeostatic mechanisms (17)(18)(19).Ocular dominance plasticity in V1 is associated with initial pruning and later formation and stabilization of spines (20,21) and occurs predominantly during a critical period of development. Maturation of the extracellular matrix is a major factor in ending the critical period, probably by increasing spine and axon stability (20)(21)(22) BDNF signaling through TrkB receptors is a key player in visual plasticity (23,24). It drives the development of inhibitory innervation, an important factor in ocular dominance plasticity (25,26). BDNF is...

Understanding the complex dynamics of cardio-respiratory coupling sheds light on the underlying mechanisms governing the communication between these two physiological systems. Previous research has predominantly considered the coupling at respiratory rates slower than the heart rate and shown that respiratory oscillations lead to modulation and/or synchronization of the heart rate. Whereas the mechanisms of cardio-respiratory communication are still under discussion, peripheral nervous regulation is considered to be the predominant factor. This work offers a novel experimental design and applies the concept of instantaneous phase to detect cardio-respiratory entrainment at elevated respiration rates, close to the resting heart rate. If such 1:1 entrainment exists, it would suggest direct neuronal communication between the respiration and heart centres in the brain. We have observed 1:1 entrainment in all volunteers, with consistently longer synchronization episodes seen in physically fitter people, and demonstrated that cardio-respiratory synchronization at both low and high respiration rates is associated with a common underlying communication mechanism.

BackgroundTransgenic mice with mosaic, Golgi-staining-like expression of enhanced green fluorescent protein (EGFP) have been very useful in studying the dynamics of neuronal structure and function. In order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. However, it has been difficult to obtain reproducible expression in the same subset of neurons for direct comparison of neurons expressing different functional proteins.Principal FindingsHere we describe a Cre-transgenic line that allows reproducible expression of transgenic proteins of choice in a small number of neurons of the adult cortex, hippocampus, striatum, olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can be expressed together in the same isolated neurons. We also describe a Cre-dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed with the Cre-transgenic line, EGFP-F expression starts in the adolescent forebrain, is present in dendrites, dendritic protrusions, axons and boutons and is strong enough for acute or chronic in vivo imaging.SignificanceThis triple transgenic approach will aid the morphological and functional characterization of neurons in various Cre-dependent transgenic mice.

Cardio-respiratory synchronization is a phenomenon of particular interest-especially at a 1:1 ratio-and may give greater insight into the underlying mechanisms of cardio-respiratory communication. Synchronization of this ratio is hypothesised to occur when breathing rate exceeds heart rate, which is the premise of this research. A novel experimental design focused on guiding elevated respiration to induce the entrainment of heart rate, and produce an equivalent rise in value. Application of instantaneous phase for identification and analysis of synchronization allowed for a reliable method of measuring the interaction between these stochastic processes. We have identified 1:1 phase synchronization in all volunteers measured. Longer synchronization episodes were observed reliably in athletic individuals, corroborating previous research for spontaneous breathing. This observation suggests that cardio-respiratory synchronization at all respiration rates is associated with a common underlying communication mechanism. Furthermore, it presents cardio-respiratory synchronization as a potential future measurement of fitness and autonomic health.