Search bioRxiv⌕ Search

Biology subjects

Rokni, D.

Publications and source records attributed to Rokni, D..

7 recordsLinked to original sources

The nucleus of the lateral olfactory tract is required for learning odor-guided food avoidance

Foraging animals must continually evaluate whether potential food sources are safe to consume. Such decisions rely on both innate preferences and learned associations formed through prior experience. Consumption of a food followed by malaise or sickness leads to avoidance of that food, reflecting learned associations between sensory cues that identify a food and its negative post-ingestive consequences. Although this form of learning has been studied extensively using taste cues, taste signals arise only after oral contact, at which point exposure to potential toxins has already occurred. Olfactory cues, in contrast, provide information about potential food sources prior to consumption, yet how odors acquire aversive value remains unclear. Here, using targeted chemogenetic perturbations, we identify the nucleus of the lateral olfactory tract (NLOT), which has direct bidirectional connectivity to olfactory regions and the basolateral amygdala, as a critical circuit element for odor-aversion learning. We find that the NLOT is required for conditioned odor aversion but is dispensable for other odor-guided behaviors and for fear conditioning driven by a non-olfactory cue. Our findings identify a selective role for the NLOT in linking olfactory cues to learned aversive outcomes, that supports odor-guided behavioral decisions. Significance statementAnimals rely on smell to evaluate food safety before consuming it, yet the brain circuits that link odor cues to learned aversive outcomes remain poorly understood. Here we identify the nucleus of the lateral olfactory tract (NLOT), a largely unstudied region at the interface between olfactory and limbic circuits, as a critical and selective node for conditioned odor aversion learning. Chemogenetic perturbations of the NLOT disrupted both the acquisition and expression of odor-malaise associations, while leaving odor detection, odor discrimination, and non-olfactory fear learning intact -- revealing a previously unrecognized specialization within olfactory-amygdala circuits that supports odor-guided decisions about food safety.

neuroscience↗

A Sexually Dimorphic Neuronal Cluster in the Mouse Medial Amygdala Exhibits Binary Activation Mode Based on Male Sexual Status

Increasing scientific interest has been directed toward understanding sexual dimorphism in the brain. Although various brain structures exhibit masculine or feminine characteristics, no strictly binary anatomical feature, such as those seen in genitalia. has been identified. In this study, we identified a dense, sexually dimorphic cluster of neurons in the posterodorsal medial amygdala (MeApd), which we named DIMPLE, that exhibited a remarkable binary pattern of cFos activation. Using the TRAP2 (Targeted Recombination in Active Populations) transgenic mouse model, we found that it was consistently labeled in all females, regardless of age or sexual experience. In males, however, DIMPLE was not labeled in any of the adult virgins but was evident pre-weaning and following mating. Surgical removal of gonads (ovariectomy or orchiectomy) did not alter the labeling pattern of DIMPLE in either sex. Interestingly, a single intraperitoneal injection of prolactin, a hormone known to increase in males after mating, induced DIMPLE labeling in virgin males. However, treatment with cabergoline, a potent inhibitor of prolactin secretion, did not prevent DIMPLE labeling in females or in post-mating males. Given the established role of the MeApd in social and reproductive behaviors, we propose that DIMPLE may support neural mechanisms underlying female-typical behavior and potentially contribute to post-mating behavioral shifts in males. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/663831v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@5f414corg.highwire.dtl.DTLVardef@1b7e9e5org.highwire.dtl.DTLVardef@15cf4bdorg.highwire.dtl.DTLVardef@1c7bc95_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO Summary of DIMPLE activity during puberty and sexual status. C_FIG

neuroscience↗

Synaptic connectivity and electrophysiological properties of the nucleus of the lateral olfactory tract

The sense of smell is tightly linked to emotions, a link that is thought to rely on the direct synaptic connections between the olfactory bulb and nuclei of the amygdala. A small number of amygdaloid nuclei are the recipients of such direct input from the olfactory bulb and their unique functions are not known. Among them, the nucleus of the lateral olfactory tract (NLOT) is unique in its developmental history and gene expression. NLOT has been very little studied and consequentially its function is unknown. Furthermore, formulation of informed hypotheses about NLOT function is at this stage limited by the lack of knowledge about its connectivity and physiological properties. Here, we used pseudo-rabies tracing methods to systematically reveal monosynaptic inputs into NLOT, and adeno-associated viruses to reveal NLOT projection targets. We found that the NLOT is interconnected with several olfactory brain regions and with the basolateral amygdala. Some of these connections were reciprocal, and some showed unique interhemispheric patterns. We tested the excitable properties of NLOT neurons and the properties of each of the major synaptic inputs. We found that the NLOT receives powerful input from piriform cortex, tenia tecta, and the basolateral amygdala, but only very weak input from the olfactory bulb. When input crosses threshold, NLOT neurons respond with calcium-dependent bursts of action potentials. This integration of olfactory and amygdalar inputs suggests that NLOT plays a role in behaviors that combine smell and emotion, possibly assigning emotional value to odors. Significance statementDespite the well-known functional links between olfaction and emotions, the physiological properties of these links remain largely understudied. One major pathway by which olfactory and emotional signals interact, is via the nucleus of the lateral olfactory tract (NLOT). NLOT has been little studied and its function is yet unclear. The lack of physiological information hinders informed hypotheses. Here, we characterize the synaptic and intrinsic properties of NLOT neurons. We show that the NLOT receives converging olfactory and amygdalar inputs, and that NLOT neurons respond to input with high-rate bursts of action potentials. This suggests that the NLOT, that harbors [~]2500 cells, encodes a low-dimensional signal that is of high importance. We hypothesize that the NLOT assigns emotional value to odors.

neuroscience↗

Stimulus-induced theta band LFP oscillations format spiking outputs in the mouse accessory olfactory bulb

Social communication is crucial for survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central VNS stage is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AOB-MCs). Recent studies provided important insights about the functional properties of AOB-MCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single unit activity in the AOB while presenting natural stimuli to adult male and female mice. Our recordings reveal prominent LFP theta band oscillatory episodes with a characteristic spatial pattern across the AOB. We find that the AOB network shows varying degrees of similarity to this pattern throughout an experiment, as a function of sensory stimulation. Analysis of LFP signal polarity and single unit activity indicate that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AOB-MCs and granule cells (GCs). Notably, spike times of many AOB-MCs are constrained to the negative LFP oscillation phase, in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.

neuroscience↗

Aberrant circuitry underlying olfaction in the face of severe olfactory bulb degeneration

The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortex in these mice responded to odors normally and its neural activity sufficed to decode odor identity. We analyzed the circuitry that supports olfactory function in these mice. We found that sensory neurons express the full repertoire of olfactory receptors and their axons project primarily to the rudimentary OB, but also ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced and the morphology of their dendrites was abnormal, extending over larger regions within the OB. Glomerular organization was lost. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements that are believed to be essential for olfaction, and may explain the retention of olfaction in humans with degenerated OBs.

neuroscience↗

Paradoxical relationship between speed and accuracy in olfactory figure-background segregation

In natural settings, many stimuli impinge on our sensory organs simultaneously. Parsing these sensory stimuli into perceptual objects is a fundamental task faced by all sensory systems. Similar to other sensory modalities, increased odor backgrounds decrease the detectability of target odors by the olfactory system. The mechanisms by which background odors interfere with the detection and identification of target odors are unknown. Here we utilized the framework of the Drift Diffusion Model (DDM) to consider possible interference mechanisms in an odor detection task. We consider effects of background odors on both signal and noise in the decision-making dynamics, and show that these produce different predictions about decision accuracy and speed. To test these predictions, we trained mice to detect target odors that are embedded in random background mixtures in a two-alternative choice task. Trial duration was independent of behavioral reaction times to avoid motivating rapid responses. We found that the behavioral data is most consistent with background odors acting by adding noise to the decision-making dynamics. The added noise decreases the correct rate, but also decreases decision times, thereby creating a paradoxical relationship between speed and accuracy of target detection, where mice make faster and less accurate decisions in the presence of background odors.

neuroscience↗

Reliable readout of mixture components from small populations of piriform cortical neurons

Coding of odorous stimuli has been mostly studied using single isolated stimuli. However, a single sniff of air in a natural environment is likely to introduce airborne chemicals emitted by multiple objects into the nose. The olfactory system is therefore faced with the task of segmenting odor mixtures to identify objects in the presence of rich and often unpredictable backgrounds. The piriform cortex is thought to be the site of object recognition and scene segmentation, yet the nature of its responses to odorant mixtures is largely unknown. In this study, we asked two related questions. 1) How are mixtures represented in the piriform cortex? And 2) Can the identity of individual mixture components be read out from mixture representations in the piriform cortex? To answer these questions, we recorded single unit activity in the piriform cortex of naive mice while sequentially presenting single odorants and their mixtures. We find that a normalization model explains mixture responses well, both at the single neuron, and at the population level. Additionally, we show that mixture components can be identified from piriform cortical activity by pooling responses of a small population of neurons - in many cases a single neuron is sufficient. These results indicate that piriform cortical representations are well suited to perform figure-background segmentation without the need for learning.

neuroscience↗