Sensory information may be represented in the brain by stereotyped mapping of axonal inputs or by patterning that varies between individuals. In olfaction, a stereotyped map is evident in the first sensory processing centre, the olfactory bulb (OB), where different odours elicit activity in unique combinatorial patterns of spatially invariant glomeruli. Activation of each glomerulus is relayed to higher cortical processing centres by a set of ∼20-50 'homotypic' mitral and tufted (MT) neurons. In the cortex, target neurons integrate information from multiple glomeruli to detect distinct features of chemically diverse odours. How this is accomplished remains unclear, perhaps because the cortical mapping of glomerular information by individual MT neurons has not been described. Here we use new viral tracing and three-dimensional brain reconstruction methods to compare the cortical projections of defined sets of MT neurons. We show that the gross-scale organization of the OB is preserved in the patterns of axonal projections to one processing centre yet reordered in another, suggesting that distinct coding strategies may operate in different targets. However, at the level of individual neurons neither glomerular order nor stereotypy is preserved in either region. Rather, homotypic MT neurons from the same glomerulus innervate broad regions that differ between individuals. Strikingly, even in the same animal, MT neurons exhibit extensive diversity in wiring; axons of homotypic MT pairs diverge from each other, emit primary branches at distinct locations and 70-90% of branches of homotypic and heterotypic pairs are non-overlapping. This pronounced reorganization of sensory maps in the cortex offers an anatomic substrate for expanded combinatorial integration of information from spatially distinct glomeruli and predicts an unanticipated role for diversification of otherwise similar output neurons.
"ssion , but also rapid toxicity . They have been used in cases where this rapid , high expression is desirable ( Bredenbeek et al . , 1993 ; de Hoop et al . , 1994 ; Gwag et al . , 1998 ; Ehrengruber et al . , 1999 ) . For example , they have been used for robust labeling of a small number of axons of neurons near the injection site in the brain ( Ghosh et al . , 2011 ; Kuramoto et al . , 2015 ) , as well as for delivering genes to neurons ( including a fluorescent tag for visualization ) for single - cell electrophysiological experiments ( Kopec et al . , 2007 ; Malinow et al . , 2010 ) , among others . However , rapid toxicity limits the use of these vectors . The fast expression and toxicity of th"
[Show abstract][Hide abstract] ABSTRACT: The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending t
Frontiers in Neuroanatomy 05/2015; 9:80. DOI:10.3389/fnana.2015.00080 · 3.54 Impact Factor
"The finding that the male and female stimuli activate different parts of the PIR and ENT areas suggests that topologically distinct MOB cortical outputs may discriminate the sexspecific stimuli. This dorsoventral separation is an example of a novel spatial organization in the piriform cortex, which until now has been considered to lack gross sensory input-based topology (Ghosh et al., 2011; Sosulski et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Central to the understanding of brain functions is insight into the distribution of neuronal activity that drives behavior. Local measurements of brain activity in behaving mice can be made with electrodes and fluorescent calcium indicators (Buzsáki, 2004 and Grewe and Helmchen, 2009), but such approaches provide information regarding only a very small fraction of the ∼70 million neurons that comprise the mouse brain. The detection of elevated levels of the immediate-early genes (IEGs) linked to recent neuronal activity (Clayton, 2000 and Guzowski et al., 2005) is a more spatially comprehensive technique. While it lacks the time resolution of electrophysiological recordings or calcium imaging, it does have the potential of providing a complete view of recent whole-brain activity. Once determined, the whole-brain IEG-based map can be used to generate structure-function hypotheses to be probed by high-resolution recordings as well as optogenetic and chemogenetic methods (Fenno et al., 2011 and Lee et al., 2014).
"There is evidence that some of the OT does not reach the bulbs directly via these neural projections (Yu et al., 1996a; Yu et al., 1996b), and transport of OT via the cerebrospinal fluid is possibly one of the mechanisms involved (Veening et al., 2010; Veening and Olivier, 2013). OT can directly affect neuronal processing in the bulb itself and in addition many amygdaloid and other limbic brain areas contain OT-receptors (Ghosh et al., 2011; Gimpl and Fahrenholz, 2001; Kang et al., 2009; 2011; Miyamichi et al., 2011; Nagayama et al., 2010; Sosulski et al., 2011) and may be influenced by a local release of OT. Similar mechanisms have been studied extensively in sheep (Kendrick, 2000; Kendrick et al., 1997; Kendrick et al., 1986; Kendrick et al., 1991). "
[Show abstract][Hide abstract] ABSTRACT: Oxytocin (OT) is a nonapeptide with an impressive variety of physiological functions. Among them, the 'prosocial' effects have been discussed in several recent reviews, but the direct effects on male and female sexual behavior did receive much less attention so far. As our contribution to honor the lifelong interest of Berend Olivier in the control mechanisms of sexual behavior, we decided to explore the role of OT in the present review. In the successive sections, some physiological mechanisms and the 'pair-bonding' effects of OT will be discussed, followed by sections about desire, female appetitive and copulatory behavior, including lordosis and orgasm. At the male side, the effects on erection and ejaculation are reviewed, followed by a section about 'premature ejaculation' and a possible role of OT in its treatment. In addition to OT, serotonin receives some attention as one of the main mechanisms controlling the effects of OT. In the succeeding sections, the importance of OT for 'the fruits of labor' is discussed, as it plays an important role in both maternal and paternal behavior. Finally, we pay attention to an intriguing brain area, the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), apparently functioning in both sexual and aggressive behavior, which are at first view completely opposite behavioral systems.
European Journal of Pharmacology 07/2014; 753. DOI:10.1016/j.ejphar.2014.07.045 · 2.53 Impact Factor
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