Biomedical subjects

Zachary F Mainen

Publications and source records attributed to Zachary F Mainen.

9 recordsLinked to original sources

PubMed2006

Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake.

Functional imaging signals arise from metabolic and hemodynamic activity, but how these processes are related to the synaptic and electrical activity of neurons is not well understood. To provide insight into this issue, we used in vivo imaging and simultaneous local pharmacology to study how sensory-evoked neural activity leads to intrinsic optical signals (IOS) in the well-defined circuitry of the olfactory glomerulus. Odor-evoked IOS were tightly coupled to release of glutamate and were strongly modulated by activation of presynaptic dopamine and GABA-B receptors. Surprisingly, IOS were independent of postsynaptic transmission through ionotropic or metabotropic glutamate receptors, but instead were inhibited when uptake by astrocytic glutamate transporters was blocked. These data suggest that presynaptic glutamate release and uptake by astrocytes form a critical pathway through which neural activity is linked to metabolic processing and hence to functional imaging signals.

Animals↗

PubMed2006

Representation of spatial goals in rat orbitofrontal cortex.

The orbitofrontal cortex (OFC) is thought to participate in making and evaluating goal-directed decisions. In rodents, spatial navigation is a major mode of goal-directed behavior, and anatomical and lesion studies implicate the OFC in spatial processing, but there is little direct evidence for coding of spatial or motor variables. Here, we recorded from ventrolateral and lateral OFC in an odor-cued two-alternative choice task requiring orientation and approach to spatial goal ports. In this context, over half of OFC neurons encoded choice direction or goal port location. A subset of neurons was jointly selective for the trial outcome and port location, information useful for the selection or evaluation of spatial goals. These observations show that the rodent OFC not only encodes information relating to general motivational significance, as shown previously, but also encodes spatiomotor variables needed to define specific behavioral goals and the locomotor actions required to attain them.

Action Potentials↗

PubMed2006

Behavioral analysis of olfactory coding and computation in rodents.

Behavioral analysis is essential to understand how the olfactory system transforms chemosensory signals into information that can be used to guide actions. Recent studies in rodents have begun to address the behavioral relevance of putative olfactory codes and computations including spatial maps, oscillatory synchrony, and evolving temporal codes. To date, these studies have failed to find support for a role of any of these mechanisms in odor discrimination. Progress calls for experiments using precise psychophysical methods in conjunction with neural recording or perturbation, in addition to ethologically minded exploration of more complex forms of odor-guided behavior.

Action Potentials↗

PubMed2006

Seeing at a glance, smelling in a whiff: rapid forms of perceptual decision making.

Intuitively, decisions should always improve with more time for the accumulation of evidence, yet psychophysical data show a limit of 200-300 ms for many perceptual tasks. Here, we consider mechanisms that favour such rapid information processing in vision and olfaction. We suggest that the brain limits some types of perceptual processing to short, discrete chunks (for example, eye fixations and sniffs) in order to facilitate the construction of global sensory images.

Animals↗

PubMed2006

Early events in olfactory processing.

Olfactory space has a higher dimensionality than does any other class of sensory stimuli, and the olfactory system receives input from an unusually large number of unique information channels. This suggests that aspects of olfactory processing may differ fundamentally from processing in other sensory modalities. This review summarizes current understanding of early events in olfactory processing. We focus on how odors are encoded by the activity of primary olfactory receptor neurons, how odor codes may be transformed in the olfactory bulb, and what relevance these codes may have for downstream neurons in higher brain centers. Recent findings in synaptic physiology, neural coding, and psychophysics are discussed, with reference to both vertebrate and insect model systems.

Animals↗

PubMed2005

The sniff as a unit of olfactory processing.

Sniffing is a rhythmic motor process essential for the acquisition of olfactory information. Recent behavioral experiments show that using a single sniff rats can accurately discriminate between very similar odors and fail to improve their accuracy by taking multiple sniffs. This implies that each sniff has the potential to provide a complete snapshot of the local olfactory environment. The discrete and intermittent nature of sniffing has implications beyond the physical process of odor capture as it strongly shapes the flow of information into the olfactory system. We review electrophysiological studies-primarily from anesthetized rodents-demonstrating that olfactory neural responses are coupled to respiration. Hence, the "sniff cycle" might play a role in odor coding, by allowing the timing of spikes with respect to the phase of the respiration cycle to encode information about odor identity or concentration. We also discuss behavioral and physiological results indicating that sniffing can be dynamically coordinated with other rhythmic behaviors, such as whisking, as well as with rhythmic neural activity, such as hippocampal theta oscillations. Thus, the sniff cycle might also facilitate the coordination of the olfactory system with other brain areas. These converging lines of empirical data support the notion that each sniff is a unit of olfactory processing relevant for both neural coding and inter-areal coordination. Further electrophysiological recordings in behaving animals will be necessary to assess these proposals.

Animals↗

PubMed2005

Dendrodendritic synaptic signals in olfactory bulb granule cells: local spine boost and global low-threshold spike.

In the mammalian olfactory bulb, axonless granule cells process synaptic input and output reciprocally within large spines. The nature of the calcium signals that underlie the presynaptic and postsynaptic function of these spines is mostly unknown. Using two-photon imaging in acute rat brain slices and glomerular stimulation of mitral/tufted cells, we observed two forms of action potential-independent synaptic Ca2+ signals in granule cell dendrites. Weak activation of mitral/tufted cells produced stochastic Ca2+ transients in individual granule cell spines. These transients were strictly localized to the spine head, indicating a local passive boosting or spine spike. Ca2+ sources for these local synaptic events included NMDA receptors, voltage-dependent calcium channels, and Ca2+-induced Ca2+ release from internal stores. Stronger activation of mitral/tufted cells produced a low-threshold Ca2+ spike (LTS) throughout the granule cell apical dendrite. This global spike was mediated by T-type Ca2+ channels and represents a candidate mechanism for subthreshold lateral inhibition in the olfactory bulb. The coincidence of local input and LTS in the spine resulted in summation of local and global Ca2+ signals, a dendritic computation that could endow granule cells with subthreshold associative plasticity.

Action Potentials↗

PubMed2003

Speed and accuracy of olfactory discrimination in the rat.

The sense of smell is typically thought of as a 'slow' sense, but the true temporal constraints on the accuracy of olfactory perception are not known. It has been proposed that animals make finer odor discriminations at the expense of additional processing time. To test this idea, we measured the relationship between the speed and accuracy of olfactory discrimination in rats. We found that speed of discrimination was independent of odor similarity, as measured by overlap of glomerular activity patterns. Even when pushed to psychophysical limits using mixtures of two odors, rats needed to take only one sniff (<200 ms at theta frequency) to make a decision of maximum accuracy. These results show that, for the purpose of odor quality discrimination, a fully refined olfactory sensory representation can emerge within a single sensorimotor or theta cycle, suggesting that each sniff can be considered a snapshot of the olfactory world.

Animals↗

PubMed2003

Mechanisms of lateral inhibition in the olfactory bulb: efficiency and modulation of spike-evoked calcium influx into granule cells.

Granule cells are axonless local interneurons that mediate lateral inhibitory interactions between the principal neurons of the olfactory bulb via dendrodendritic reciprocal synapses. This unusual arrangement may give rise to functional properties different from conventional lateral inhibition. Although granule cells spike, little is known about the role of the action potential with respect to their synaptic output. To investigate the signals that underlie dendritic release in these cells, two-photon microscopy in rat brain slices was used to image calcium transients in granule cell dendrites and spines. Action potentials evoked calcium transients throughout the dendrites, with amplitudes increasing with distance from soma and attaining a plateau level within the external plexiform layer, the zone of granule cell synaptic output. Transient amplitudes were, on average, equal in size in spines and adjacent dendrites. Surprisingly, both spine and dendritic amplitudes were strongly dependent on membrane potential, decreasing with depolarization and increasing with hyperpolarization from rest. Both the current-voltage relationship and the time course of inactivation were consistent with the known properties of T-type calcium channels, and the voltage dependence was blocked by application of the T-type calcium channel antagonists Ni2+ and mibefradil. In addition, mibefradil reduced action potential-mediated synaptic transmission from granule to mitral cells. The implication of a transiently inactivating calcium channel in synaptic release from granule cells suggests novel mechanisms for the regulation of lateral inhibition in the olfactory bulb.

Action Potentials↗