Article

Cortical representation of olfactory input by trans-synaptic tracing

HHMI/Department of Biology, Stanford University, Stanford, California 94305, USA.
Nature (Impact Factor: 41.46). 12/2010; 472(7342):191-6. DOI: 10.1038/nature09714
Source: PubMed

ABSTRACT

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.

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    • "Indeed, anatomical tracing studies show that individual anterior piriform cortex (APC) feedback axons follow long, tortuous trajectories across the OB and form clusters of synapses that can lie far apart from each other (Matsutani, 2010). The output neurons of the OB, the mitral/tufted (MT) cells, project most abundantly in a distributed manner to the piriform cortex and to several other areas including the AON, olfactory tubercle , entorhinal cortex, and amygdala (Ghosh et al., 2011; Miyamichi et al., 2011; Nagayama et al., 2010; Shepherd, 1972; Sosulski et al., 2011). In turn, the primary recipients of these feedback projections are the granule cells (GCs) (Balu et al., 2007; Boyd et al., 2012; Margrie et al., 2001; Urban and Sakmann, 2002; Wilson and Mainen, 2006). "
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    • "Note that the volumes of injected virus were small (150 nL) to restrict the number of starter cells and the location of starter cells to a local region of visual cortex, permitting connections within visual cortex to be analyzed. In addition, to validate this retrograde tracing method, which previously had only been used for long distance connectivity (Miyamichi et al. 2011), in one additional experiment, much larger injections were made (1000 nL of each virus) and retrograde labeling in LGN and contralateral visual cortex was assessed. Five days after the modified rabies injection (P40–P42), animals were deeply anesthetized and perfused with ice-cold PBS and 4% paraformaldehyde . "
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    • "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). "
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