Olfaction is often studied in the context of learning and memory. Interestingly, very few reports have appeared that describe synaptic plasticity associated with learning and memory in other systems, such as spike-timing-dependent synaptic modulation or structural dendritic plasticity in the olfactory bulb/antennal lobe. Nevertheless, experience-related plasticity is observed at multiple levels. For example, prenatal exposure of pregnant mothers to food odors causes enhanced sensory responses to these odors in pups after birth, and supervised and nonsupervised plasticity mechanisms can change odor-evoked spatial or temporal activity patterns in the olfactory bulb/antennal lobe (Freeman and Schneider 1982; Kendrick et al. 1992; Faber et al. 1999; Stopfer and Laurent 1999). The olfactory bulb/antennal lobe receives centrifugal inputs that express neuro-modulators (acetylcholine, serotonin, and norepinephrine in vertebrates and octopamine, dopamine, and serotonin in insects). These neuromodulators act at different sites and may modulate the function of olfactory microcircuits in a concerted fashion (e.g., Castillo et al. 1999). Noradrenergic inputs have, in particular, been implicated in the local modulation of dendrodendritic synaptic microcircuits between mitral and granule cells in the context of olfactory memory formation (Kendrick et al. 1992). In insects, octopamine and dopamine are likely to be important neuromodulators in the antennal lobe and higher brain regions (Hammer and Menzel 1998; Schwaerzel et al. 2003).
A remarkable feature of the vertebrate olfactory system is the lifelong turnover of both OSNs and interneurons in the olfactory bulb (see Lledo, this volume). Neuronal turnover is not observed in the olfactory system of invertebrates, possibly because their lifespan is usually much shorter. The life span of a mature vertebrate OSN is about 90 days but can be prolonged to 12 months under certain conditions, indicating that it is regulated by environmental factors.
Blocking airflow through one naris reduces the formation of new neurons, raising the question as to which mechanisms control stem cell proliferation. One obvious role of ongoing turnover of OSNs is the replacement of OSNs that have been damaged by exposure to pathogens or otherwise. It is currently unknown whether the turnover of OSNs can also contribute to the adaptation of individuals to slow changes of the natural odor space.
Within the adult olfactory bulb, interneurons are continuously replaced by new neurons that originate from the subventricular zone and migrate to the olfactory bulb in the rostral migratory stream. In the embryo, bulbar interneurons are derived from neuronal precursors in a different proliferation zone, the lateral ganglionic eminences. Up to 80,000 new neurons arrive in the adult olfactory bulb every day, and ~1% of the granule cells are turning over at each moment. Conceivably, the turnover of neurons in the adult olfactory bulb could modify the function of olfactory microcircuits in important ways, on a timescale of weeks. Moreover, it is an interesting question how the function of olfactory microcircuits is maintained during the continuous integration of new neurons. New neurons in the olfactory bulb gradually mature over a period of ~ 4 weeks. However, under normal conditions, ~50% of the newborn neurons will undergo apoptosis within a few days following their integration in the network. The rate of apoptosis, but not the rate of turnover, depends on external factors (see below). Hence, the addition of new neurons to the olfactory bulb can be regulated by modulating neuron survival.
If newborn interneurons are necessary for bulbar function or plasticity, disruption of cell migration in the rostral migratory stream would be expected to affect olfactory processing or learning. Indeed, in PSA-NCAM-mutant mice, the number of newborn granule cells is reduced by ~ 40% and odor discrimination is impaired (Gheusi et al. 2000). One hypothesis is that the impairment is due to reduced GABAergic inhibition of mitral cells by granule cells, which is likely to play a role in the function of interglomerular microcircuits (see above). Furthermore, the rate of apoptosis is reduced in animals exposed to an enriched olfactory environment. This effect is associated with more robust and extended long-term memory measured in a simple task. In general, these results suggest a relationship between interneuron number and system performance.
The maturation of adult-generated neurons does not recapitulate the maturation of the same interneuron types during embryogenesis (Carleton et al. 2003). An important difference in the maturation of granule cells is that Na+ channels conferring spiking activity are expressed early during maturation in the embryo but appear very late in the maturation of adult-generated granule cells. This may be a mechanism to prevent the interference of immature granule cells with the functional circuits already in place. An important step in the maturation of newborn neurons is the exit from the rostral migratory stream into the granule cell layer of the olfactory bulb. Because migration is predominantly radial after leaving the rostral migratory stream, this step determines the region where the new neuron will be integrated. Exit from the rostral migratory stream is blocked by NMDA receptor antagonists, raising the possibility that the recruitment of newborn neurons is site-specific and regulated by activity in the olfactory bulb. Ongoing experiments, therefore, address the question of whether sensory experience or odor learning may recruit newborn neurons specifically to those microcircuits that participate in the relevant behavior.
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