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


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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    ABSTRACT: The olfactory bulb receives rich glutamatergic projections from the piriform cortex. However, the dynamics and importance of these feedback signals remain unknown. Here, we use multiphoton calcium imaging to monitor cortical feedback in the olfactory bulb of awake mice and further probe its impact on the bulb output. Responses of feedback boutons were sparse, odor specific, and often outlasted stimuli by several seconds. Odor presentation either enhanced or suppressed the activity of boutons. However, any given bouton responded with stereotypic polarity across multiple odors, preferring either enhancement or suppression. Feedback representations were locally diverse and differed in dynamics across bulb layers. Inactivation of piriform cortex increased odor responsiveness and pairwise similarity of mitral cells but had little impact on tufted cells. We propose that cortical feedback differentially impacts these two output channels of the bulb by specifically decorrelating mitral cell responses to enable odor separation. Copyright © 2015 Elsevier Inc. All rights reserved.
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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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    ABSTRACT: Synapse pruning is an activity-regulated process needed for proper circuit sculpting in the developing brain. Major histocompatibility class I (MHCI) molecules are regulated by activity, but little is known about their role in the development of connectivity in cortex. Here we show that protein for 2 MHCI molecules H2-Kb and H2-Db is associated with synapses in the visual cortex. Pyramidal neurons in mice lacking H2-Kb and H2-Db (KbDb KO) have more extensive cortical connectivity than normal. Modified rabies virus tracing was used to monitor the extent of pyramidal cell connectivity: Horizontal connectivity is greater in the visual cortex of KbDb KO mice. Basal dendrites of L2/3 pyramids, where many horizontal connections terminate, are more highly branched and have elevated spine density in the KO. Furthermore, the density of axonal boutons is elevated within L2/3 of mutant mice. These increases are accompanied by elevated miniature excitatory postsynaptic current frequency, consistent with an increase in functional synapses. This functional and anatomical increase in intracortical connectivity is also associated with enhanced ocular dominance plasticity that persists into adulthood. Thus, these MHCI proteins regulate sculpting of local cortical circuits and in their absence, the excess connectivity can function as a substrate for cortical plasticity throughout life.
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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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