Non-topographical contrast enhancement in the olfactory bulb

Abstract

Background: Contrast enhancement within primary stimulus representations is a common feature of sensory systems that regulates the discrimination of similar stimuli. Whereas most sensory stimulus features can be mapped onto one or two dimensions of quality or location (e.g., frequency or retinotopy), the analogous similarities among odor stimuli are distributed highdimensionally, necessarily yielding a chemotopically fragmented map upon the surface of the olfactory bulb. While olfactory contrast enhancement has been attributed to decremental lateral inhibitory processes among olfactory bulb projection neurons modeled after those in the retina, the two-dimensional topology of this mechanism is intrinsically incapable of mediating effective contrast enhancement on such fragmented maps. Consequently, current theories are unable to explain the existence of olfactory contrast enhancement.

Relational representation in the olfactory system

“…In concert with related glomerular processing circuitry (22,36), this mechanism enables functional interpretation of observations that odors commonly evoke inhibitory responses in mitral cells and that increasing odorant concentrations do not monotonically increase spike rates in mitral cells (29), setting the stage for subsequent processing by the mitral-granule cell network (35,37). Moreover, behavioral assays confirm that normalized olfactory representations predict perceptual relationships across concentrations, whereas raw glomerular representations do not.…”

“…The computation of intensity-independent stimulus representations in sensory systems depends on the existence of associated inhibitory systems that are activated more broadly by sensory stimuli than are the principal neurons receiving direct sensory inputs (22)(23)(24). Specifically, inhibition that is uniformly distributed across the input field, perhaps representing an average or sum of all input activity, will tend to preserve the pattern of relative activation levels across the field irrespective of total intensity, whereas inhibition that is delivered in proportion to local activation levels, or in an otherwise biased manner, will retain concentration-dependent distortions in the resulting output patterns.…”

“…Specifically, inhibition that is uniformly distributed across the input field, perhaps representing an average or sum of all input activity, will tend to preserve the pattern of relative activation levels across the field irrespective of total intensity, whereas inhibition that is delivered in proportion to local activation levels, or in an otherwise biased manner, will retain concentration-dependent distortions in the resulting output patterns. Recent work in the OB (25,26) has identified an interconnected network of excitatory juxtaglomerular interneurons, external tufted (ET) and short-axon (SA) cells, that delivers inhibition onto OB principal neurons (mitral cells) via local inhibitory neurons [periglomerular (PG) cells], and it has been suggested that this recurrent excitatory network mediates the uniform inhibition required for concentration-invariant secondary representations and other odor-processing mechanisms (22). We show here that this interglomerular excitatory network, via activation of local inhibitory neurons and with estimates of synaptic densities and connectivity derived from experimental Author contributions: T.A.C., B.A.J., M.L., and C.L.…”

D-beta-hydroxybutyrate extends lifespan in C. elegans

“…A ketogenic diet has been shown to delay loss of motor performance and loss of spinal cord motor neurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis (ALS) [68]. So lastly, we performed experiments using worms overexpressing human TDP-43 [69], which forms insoluble aggregates in the nervous system of patients with ALS and other neuro-degenerative disorders [70] and when expressed in the nervous system of worms [69].…”

“…Therefore, βHB either stabilized complex I function in the presence of rotenone or stimulated complex II-dependent respiration to bypass this block of complex I function. In mammals βHB has been shown to stabilize and increase the efficiency of ETC complex I [68, 79]. The increased rate of NADH oxidation in the presence of βHB led to decreased ROS levels in mouse neocortical neurons following glutamate excitotoxicity [79].…”