Olfactory Processing and Associative Memory: Cellular and Modeling Studies

A hunger for odour: Leptin modulation of olfaction.

In colonies of eusocial Hymenoptera cooperation is organized through social odors, and particularly ants rely on a sophisticated odor communication system. Neuronal information about odors is represented in spatial activity patterns in the primary olfactory neuropile of the insect brain, the antennal lobe (AL), which is analog to the vertebrate olfactory bulb. The olfactory system is characterized by neuroanatomical compartmentalization, yet the functional significance of this organization is unclear. Using two-photon calcium imaging, we investigated the neuronal representation of multicomponent colony odors, which the ants assess to discriminate friends (nestmates) from foes (nonnestmates). In the carpenter ant Camponotus floridanus, colony odors elicited spatial activity patterns distributed across different AL compartments. Activity patterns in response to nestmate and nonnestmate colony odors were overlapping. This was expected since both consist of the same components at differing ratios. Colony odors change over time and the nervous system has to constantly adjust for this (template reformation). Measured activity patterns were variable, and variability was higher in response to repeated nestmate than to repeated nonnestmate colony odor stimulation. Variable activity patterns may indicate neuronal plasticity within the olfactory system, which is necessary for template reformation. Our results indicate that information about colony odors is processed in parallel in different neuroanatomical compartments, using the computational power of the whole AL network. Parallel processing might be advantageous, allowing reliable discrimination of highly complex social odors.

Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed. Clinical Coma Recovery Scale - Revised (CRS-R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome (n = 26) patients, minimally conscious state (n = 7) patients and healthy controls (n = 25). A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients' etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor-related activity in the orbitofrontal cortex and CRS-R scores. It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.

The gaseous neurotransmitters nitric oxide (NO) and carbon monoxide (CO) are prominent and universal components of the array of neurotransmitters found in olfactory information processing systems. These highly mobile communication compounds have effects on both second messenger signaling and directly on ion channel gating in olfactory receptors and central synaptic processing of receptor input. Olfactory systems are notable for the plasticity of their synaptic connections, revealed both in higher-order associative learning mechanisms using odor cues and developmental plasticity operating to maintain function during addition of new olfactory receptors and new central olfactory interneurons. We use the macrosmatic terrestrial mollusk Limax maximus to investigate the role of NO and CO in the dynamics of central odor processing and odor learning. The major central site of odor processing in the Limax CNS is the procerebral (PC) lobe of the cerebral ganglion, which displays oscillatory dynamics of its local field potential and periodic activity waves modulated by odor input. The bursting neurons in the PC lobe are dependent on local NO synthesis for maintenance of bursting activity and wave propagation. New data show that these bursting PC interneurons are also stimulated by carbon monoxide. The synthesizing enzyme for carbon monoxide, heme oxygenase 2, is present in the neuropil of the PC lobe. Since the PC lobe exhibits two forms of synaptic plasticity related to both associative odor learning and continual connection of new receptors and interneurons, the use of multiple gaseous neurotransmitters may be required to enable these multiple forms of synaptic plasticity.

Neural correlates of olfactory processing in congenital blindness

Karst aquifers are heterotrophic ecosystems fueled by organic matter imported from the surface. The temporal pattern of floods influences organic matter import and the spatial distribution of organic matter and biofilms in aquifer structural zones. We investigated spatial and temporal patterns of bacterial density and activity as indicators of energy availability and microbial dynamics in a karst aquifer. During baseflow, bacterial density and microbial hydrolytic activity were similar in the upper and lower zones of the aquifer. Floods apparently scoured aquifer biofilms and transported soil bacteria into the aquifer, increasing inactive bacterial density in the water column. Respiring bacterial density did not respond to floods and changed little over time. The overall proportion of total bacteria that were respiring was very high on some dates, resulting from a reduction of inactive cell density during flood recession. Floods appear to be key events in scouring senescent microbial assemblages in karst aquifers and stimulating microbial recolonization of the aquifer matrix. We conclude that a conceptual model of karst aquifer structure and function should incorporate changes caused by alternation between flooding and drying in the aquifer.

The study of ecological and behavioral aspects of anuran reproduction is fundamental for the understanding of the evolution of life history traits. In this study we present the temporal and spatial patterns of reproductive activity in Rhinella hoogmoedi, as well as the description of its advertisement call, in a population from a remnant of tropical rainforest in Northeastern Brazil. Calling activity began before the start of the rainy season and lasted from November to April; vocalization activity was not correlated with the amount of rainfall. Reproductive males called on a variety of substrates close to or in permanent or temporary water bodies, during both day and night. Male behavior at high and low densities, calling sites occupancy and reproductive period indicate an unusual explosive breeding pattern for the species. Rhinella hoogmoedi presented a multi-pulsed call, composed of pulse group calls, similar to Rhinella paraguayensis, Rhinella castaneotica, Rhinella martyi, populations of Rhinella gr. margaritifera from Bolivia, Rhinella margaritifera from French Guyana, and Rhinella gr. margaritifera from Cusco, Peru. Acoustic parameters such as call duration, number of pulse groups per call, number of calls per minute, note duration, number of notes per minute, pulse rate, dominant frequency, and amplitude modulation types of call, were good parameters to discriminate among the species of the Rhinella margaritifera group, as in the members of the Bufonidae family. New descriptions of complete advertisement calls and molecular studies will help elucidate taxonomic, biogeographic, and phylogenic patterns for this complex of species.

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation.

1. Neonatal rat pups were classically conditioned to an odor stimulus from postnatal day 1 (PN1) to PN18. Tactile stimulation (stroking) was used as the unconditioned stimulus. On PN19, mitral/tufted cell single-unit responses to the conditioned odor were examined in both conditioned and control pups. Recordings were made from mitral/tufted cells in two regions of the olfactory bulb: 1) an area typically associated with focal [14C]2-deoxyglucose (2-DG) uptake in response to the conditioned odor and 2) an area distant from focal 2-DG uptake to the conditioned odor. Animals were anesthetized with urethane and were naturally respiring during the single-unit recording procedure. 2. Changes in mitral/tufted cell firing rate in response to odors in both bulbar regions and all training groups were classified as either excitatory, suppressive, or no response. This response classification was used to compare response patterns to the conditioned odor between bulbar regions and training groups. 3. Classical conditioning selectively modified the response patterns of mitral/tufted cells to the conditioned odor when those cells were associated with regions of focal 2-DG uptake for that odor. Mitral/tufted cells demonstrated significantly more suppressive and fewer excitatory responses to the conditioned odor than cells in control pups. Response patterns to a novel odor were not similarly modified. 4. Response patterns of mitral/tufted cells distant from the focal region of 2-DG uptake to the conditioned odor were not modified by conditioning compared with control pups. 5. The difference in response pattern between cells in the 2-DG focus and cells distant to the 2-DG focus was apparent within 500 ms of the stimulus onset. Given the respiratory rate of these pups (2 Hz), these data suggest that the modified response pattern occurred on the first inhalation of the learned odor. 6. These data demonstrate that both spatial and temporal patterns of olfactory bulb output neuron activity are used in the coding of olfactory information in the bulb. Furthermore, these spatial/temporal response patterns can be modified by early learning.

Natural olfactory stimuli are often complex mixtures of volatiles, of which the identities and ratios of constituents are important for odor-mediated behaviors. Despite this importance, the mechanism by which the olfactory system processes this complex information remains an area of active study. In this review, we describe recent progress in how odorants and mixtures are processed in the brain of insects. We use a comparative approach toward contrasting olfactory coding and the behavioral efficacy of mixtures in different insect species, and organize these topics around four sections: (1) Examples of the behavioral efficacy of odor mixtures and the olfactory environment; (2) mixture processing in the periphery; (3) mixture coding in the antennal lobe; and (4) evolutionary implications and adaptations for olfactory processing. We also include pertinent background information about the processing of individual odorants and comparative differences in wiring and anatomy, as these topics have been richly investigated and inform the processing of mixtures in the insect olfactory system. Finally, we describe exciting studies that have begun to elucidate the role of the processing of complex olfactory information in evolution and speciation.

To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural activity was mapped across the entire glomerular layer by using the ¿(14)C2-deoxyglucose method. Group responses were averaged and compared by using data matrices. The glomerular activity patterns that resulted from this analysis were comprised of modules. Unique combinations of modules were activated by each odorant, demonstrating what may be part of the neural code for odorants. Most of the modules were clustered together in the bulb, perhaps providing for enhanced contrast between related chemicals by means of lateral inhibition. We also determined whether changes in odorant concentration would affect spatial patterns of glomerular activity. Two odorants, pentanal and 2-hexanone, evoked different patterns at increased concentrations, with additional glomeruli being recruited at a great distance from glomeruli in which activity was evoked at lower concentrations. Humans report that both of these odorants change in perceived odor with increasing concentration. Three other odorants (pentanoic acid, methyl pentanoate, and pentanol) did not recruit new areas of glomerular activation with increasing concentration, and humans do not report a changed odor across concentrations of these odorants. The results suggest that changes in modular glomerular activity patterns could underlie altered odor perception across odorant concentrations, and they provide additional support for a combinatorial, spatially based code in the olfactory system.

The authors examine facial emotion recognition and unirhinal olfactory performance in 19 schizophrenia patients and 14 comparison subjects. In patients, right nostril odor identification performance was positively related to overall emotion recognition accuracy, specifically, sad facial expressions. Olfactory and emotion recognition abilities appear significantly linked in schizophrenia.

Olfactory system and energy metabolism: a two-way street

By finding broader temporal and spatial patterns of brain activity, dictionary learning and sparse coding techniques circumvent the constraints of typical voxel-level studies of task-based functional magnetic resonance imaging (fMRI) data. Prior applications of these algorithms to task-related fMRI data, on the other hand, have not been tuned to simultaneously uncover temporal patterns of activity that change in tandem with changes in task circumstances and spatial patterns that exploit existing neuroscience knowledge. This work, presents a sparse dictionary learning method that decomposes fMRI data into temporal patterns of signals that loosely differ between task conditions and sparse spatial patterns that are at least partially similar to known functional network hubs, based on prior knowledge of the temporal pattern of task conditions and the locations of brain regions hypothesized to be involved in the task. To over come the a major drawback of the prior work in terms being constrained to provide an equal number of spatial and temporal patterns, even when the data was more accurately represented by a larger number spatial than temporal patterns (or vice versa), this work also propose a constrained decoupled dictionary learning method that uses prior knowledge related to task paradigms and the spatial locations of task-related brain regions to estimate decoupled spatial and temporal patterns that represent the fMRI data. The utility of sparse dictionary learning methods applied to task fMRI data is increased by simultaneously exploiting the task's known temporal structure and biasing solutions towards putative network hubs. The method identifies a high percentage of the spatial and temporal patterns programmed into simulated fMRI data. The temporal and spatial patterns are identified using an effective on-line optimization methodology. The technique detects geographical and temporal patterns in synthetic task fMRI data. When applied to two real-world fMRI data sets, the method: 1. automatically identifies temporal and spatial patterns that were known by neuroscientists to be task-related a priori but were not provided as inputs to the method; 2. provides measurements that differ significantly between differing tasks. When applied to real fMRI data from 100 participants two different studies, the suggested method also identifies geographic regions known a priori to be engaged by the Attention Network Task (ANT), AX-Continuous Performance Task (AX-CPT) and Stroop Task more thoroughly than competing methods. Using task information to partially constrain dictionary learning allowed this method to identify task related networks in real and synthetic fMRI data.