Gordon M. Shepherd

Dendrodendritic synaptic pathway for inhibition in the olfactory bulb

Abstract Anatomical and physiological evidence based on independent studies of the mammalian olfactory bulb points to synaptic interactions between dendrites. A theoretical analysis of electric potentials in the rabbit olfactory bulb led originally to the conclusion that mitral dendrites synaptically excite granule dendrites and granule dendrites then synaptically inhibit mitral dendrites. In an independent electron micrographic study of the rat olfactory bulb, synaptic contacts were found between granule and mitral dendrites. An unusual feature was the occurrence of more than one synaptic contact per single granule ending on a mitral dendrite; as inferred from the morphology of these synaptic contacts, a single granule ending was often presynaptic at one point and postsynaptic at an adjacent point with respect to the contiguous mitral dendrite. We postulate that these synaptic contacts mediate mitral-to-granule excitation and granule-to-mitral inhibition. These dendrodendritic synapses could provide a pathway for both lateral and self inhibition.

ModelDB: A Database to Support Computational Neuroscience

Wider dissemination and testing of computational models are crucial to the field of computational neuroscience. Databases are being developed to meet this need. ModelDB is a web-accessible database for convenient entry, retrieval, and running of published models on different platforms. This article provides a guide to entering a new model into ModelDB.

Retinal ganglion cells express a cGMP-gated cation conductance activatable by nitric oxide donors

We have identified a putative cGMP-gated cation conductance in rat retinal ganglion cells. Both in situ hybridization and polymerase chain reaction amplification detected transcripts in ganglion cells that were highly homologous to the cGMP-gated cation channel expressed in rod photoreceptors. Whole-cell patch-clamp recordings detected a current stimulated by cGMP due to activation of nonselective cation channels. This current had a reversal potential near 0 mV, showed some outward rectification, and could be blocked by Cd2+. The current could also be activated by a phosphodiesterase inhibitor and the nitric oxide donors sodium nitroprusside and S-nitrosocysteine. We propose that nitric oxide released from an identified subpopulation of amacrine cells may activate this channel to modulate ganglion cell activity.

Analysis of Relations between NMDA Receptors and GABA Release at Olfactory Bulb Reciprocal Synapses

In the mammalian olfactory bulb, signal processing is mediated by synaptic interactions between dendrites. Glutamate released from mitral cell dendrites excites dendritic spines of granule cells, which in turn release GABA back onto the mitral cell dendrites, forming a reciprocal synaptic pair. This feedback synaptic circuit was shown to be mediated predominantly by NMDA receptors. We further utilized caged Ca2+ compounds to obtain insight into the mechanism that couples NMDA receptor activation to GABA release. Feedback inhibition elicited by photo-release of caged Ca2+ in mitral cell secondary dendrites persisted when voltage-gated Ca2+ channels were blocked by cadmium (Cd2+) and nickel (Ni2+). These results indicate that Ca2+ influx through NMDA receptors can directly trigger presynaptic GABA release for local dendrodendritic feedback inhibition.

Logic operations are properties of computer-simulated interactions between excitable dendritic spines.

Neurons in the central nervous system of mammals and many other species receive most of their synaptic inputs in their dendritic branches and spines, but the precise manner in which this information is processed in the dendrites is not understood. In order to gain insight into these mechanisms, simulations of interactions between distal dendritic spines with an excitable membrane have been carried out, using an electrical circuit analysis program for the compartmental representation of a dendrite and several spines. Interactions between responses to single and paired excitatory and inhibitory synaptic inputs have been analyzed. Basic logic operations, including AND gates, OR gates and AND-NOT gates, arise from these interactions. The results suggest the computational power and precision of excitable spines in distal branches of neuronal dendrites, especially those of pyramidal neurons in the cerebral cortex. The applicability to information processing in distal dendrites is discussed.

The Olfactory Bulb

The olfactory bulb is the primary center for transmission of olfactory information to the vertebrate brain. Its functions are (1) to receive and process the information from the olfactory receptor neurons, (2) to send this information to different parts of the olfactory cortex in the forebrain, and (3) to provide for integration and modulation of the information by means of pathways from midbrain and forebrain centers.

Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones

It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high‐resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2‐Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed. J. Comp. Neurol. 489:491–500, 2005.

Organization of Heterogeneous Scientific Data Using the EAV/CR Representation

Entity-attribute-value (EAV) representation is a means of organizing highly heterogeneous data using a relatively simple physical database schema. EAV representation is widely used in the medical domain, most notably in the storage of data related to clinical patient records. Its potential strengths suggest its use in other biomedical areas, in particular research databases whose schemas are complex as well as constantly changing to reflect evolving knowledge in rapidly advancing scientific domains. When deployed for such purposes, the basic EAV representation needs to be augmented significantly to handle the modeling of complex objects (classes) as well as to manage interobject relationships. The authors refer to their modification of the basic EAV paradigm as EAV/CR (EAV with classes and relationships). They describe EAV/CR representation with examples from two biomedical databases that use it.

Suckling pheromone stimulation of a modified glomerular region in the developing rat olfactory bulb revealed by the 2-deoxyglucose method

Topographic analysis of olfactory bulb activation, based on the [14C]2-deoxy-Dglucose (2DG) autoradiographic method of Kennedy et al. s, has provided new insight into the funcitonal organization of this system. Recent experiments have shown that odor stimulation produces localized sites of activity-related glucose metabolism within the glomerular layer; and that for specific odors, such as amyl acetate and camphor, the autoradiographs reveal overlapping but distinguishable spatial patterns of enhanced uptake, which vary in a systematic fashion with odor concentra*ion14As, 17. In the present study we have extended this technique in order to examine the olfactory bulb of 9-18-day-old rats. There were two main objectives of this undertaking. First, we sought to determine whether the developing olfactory bulb would show localized uptake of 2DG in response to amyl acetate, and whether the topographical pattern of activation was similar to that seen in adults. Secondly, we wished to determine whether a specific pattern would be induced by a behaviorally-significant odor, such as a pheromone. Behavioral studies have shown that olfaction is a dominant sensory modality for nipple attachment by rat pups, and that the nipples are coated by a lipid soluble substance that must be present in order for rat pups to effectively attach to a nipple 14. Removal of this scent by chemical lavage virtually eliminates attachment in pups of all ages, whereas application of a vacuum-distilled extract of the wash fluid fully restores suckling a,19,20. Both behavioral and chemical investigations indicate that this nipple cue satisfies nearly all proposed criteria for a pheromone 2 which acts by directing and permitting nipple attachmenta,vA0,16, ~s-20. We therefore examined the 2DG patterns induced in the olfactory bulbs of rat pups during nipple attachment and suckling. The results have provided evidence for a specific activity site associated with a macroglomerular complex in rat pup olfactory bulb under these conditions.

The Human Sense of Smell: Are We Better Than We Think?

Gordon Shepherd challenges the notion - based on genetic evidence - that olfaction is less well developed in humans as compared to other mammals