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Cell Oct 2022In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By...
In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Here, we used high-throughput sequencing-based neuroanatomical techniques to analyze the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. Thus, as in other sensory modalities, olfactory information is routed at early stages of processing to functionally diverse targets in a coordinated manner.
Topics: Mice; Animals; Olfactory Pathways; Olfactory Cortex; Olfactory Bulb; Neurons; High-Throughput Nucleotide Sequencing
PubMed: 36306734
DOI: 10.1016/j.cell.2022.09.038 -
Neuron May 2022The hippocampus is essential for different forms of declarative memory, including social memory, the ability to recognize and remember a conspecific. Although recent...
The hippocampus is essential for different forms of declarative memory, including social memory, the ability to recognize and remember a conspecific. Although recent studies identify the importance of the dorsal CA2 region of the hippocampus in social memory storage, little is known about its sources of social information. Because CA2, like other hippocampal regions, receives its major source of spatial and non-spatial information from the medial and lateral subdivisions of entorhinal cortex (MEC and LEC), respectively, we investigated the importance of these inputs for social memory. Whereas MEC inputs to CA2 are dispensable, the direct inputs to CA2 from LEC are both selectively activated during social exploration and required for social memory. This selective behavioral role of LEC is reflected in the stronger excitatory drive it provides to CA2 compared with MEC. Thus, a direct LEC → CA2 circuit is tuned to convey social information that is critical for social memory.
Topics: Entorhinal Cortex; Hippocampus; Mental Recall
PubMed: 35180391
DOI: 10.1016/j.neuron.2022.01.028 -
Cell and Tissue Research Jan 2021
Topics: Animals; Humans; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Mucosa; Olfactory Pathways; Olfactory Perception; Receptors, Odorant; Smell
PubMed: 33447882
DOI: 10.1007/s00441-020-03389-1 -
Nature Methods Nov 2020The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB...
The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors.
Topics: Acetylcholine; Animals; Animals, Genetically Modified; Behavior, Animal; Biosensing Techniques; Brain; Cholinergic Agents; Drosophila; Green Fluorescent Proteins; HEK293 Cells; Humans; Mice; Mushroom Bodies; Neurons; Olfactory Cortex; Receptor, Muscarinic M3; Somatosensory Cortex
PubMed: 32989318
DOI: 10.1038/s41592-020-0953-2 -
Nature Oct 2021Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning. However, it remains unclear how dopamine reward...
Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning. However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network that is crucial for learning and memory. Here, using cell-type-specific electrophysiological recording, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue-reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue-reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map.
Topics: Animals; Anticipation, Psychological; Cues; Dopamine; Entorhinal Cortex; Female; Male; Memory; Mice; Mice, Inbred C57BL; Pyramidal Cells; Reward
PubMed: 34552245
DOI: 10.1038/s41586-021-03948-8 -
Scientific Reports Feb 2021Olfactory impairment after a traumatic impact to the head is associated with changes in olfactory cortex, including decreased gray matter density and decreased BOLD...
Olfactory impairment after a traumatic impact to the head is associated with changes in olfactory cortex, including decreased gray matter density and decreased BOLD response to odors. Much less is known about the role of other cortical areas in olfactory impairment. We used fMRI in a sample of 63 participants, consisting of 25 with post-traumatic functional anosmia, 16 with post-traumatic hyposmia, and 22 healthy controls with normosmia to investigate whole brain response to odors. Similar neural responses were observed across the groups to odor versus odorless stimuli in the primary olfactory areas in piriform cortex, whereas response in the frontal operculum and anterior insula (fO/aI) increased with olfactory function (normosmia > hyposmia > functional anosmia). Unexpectedly, a negative association was observed between response and olfactory perceptual function in the mediodorsal thalamus (mdT), ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (pCC). Finally, connectivity within a network consisting of vmPFC, fO, and pCC could be used to successfully classify participants as having functional anosmia or normosmia. We conclude that, at the neural level, olfactory impairment due to head trauma is best characterized by heightened responses and differential connectivity in higher-order areas beyond olfactory cortex.
Topics: Adult; Aged; Anosmia; Brain; Brain Injuries, Traumatic; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Odorants; Olfaction Disorders; Olfactory Cortex; Olfactory Perception; Prefrontal Cortex; Smell
PubMed: 33597627
DOI: 10.1038/s41598-021-83621-2 -
Chemical Senses Jan 2021The neocortex and olfactory cortices share many features including their laminar organization, developmental sequences, and cell types. Previous work indicates that...
The neocortex and olfactory cortices share many features including their laminar organization, developmental sequences, and cell types. Previous work indicates that neocortical pyramidal cells exhibit a gradient of dendritic size: cells involved in the initial processing of information are less complex than those in subsequent, higher processing areas. Results presented here confirm that the same is true for the olfactory cortex: pyramidal cells in the region closest to the olfactory bulb, the anterior olfactory nucleus, have smaller total dendritic length and occupy less neural space than those in the posterior piriform cortex. These findings add to the evidence for general rules of development, organization, and function across forebrain cortices.
Topics: Animals; Mice; Olfactory Cortex; Pyramidal Cells
PubMed: 33433589
DOI: 10.1093/chemse/bjab002 -
ENeuro 2017The olfactory cortex is part of the mammalian cerebral cortex together with the neocortex and the hippocampus. It receives direct input from the olfactory bulbs and... (Review)
Review
The olfactory cortex is part of the mammalian cerebral cortex together with the neocortex and the hippocampus. It receives direct input from the olfactory bulbs and participates in odor discrimination, association, and learning (Bekkers and Suzuki, 2013). It is thought to be an evolutionarily conserved paleocortex, which shares common characteristics with the three-layered general cortex of reptiles (Aboitiz et al., 2002). The olfactory cortex has been studied as a "simple model" to address sensory processing, though little is known about its precise cell origin, diversity, and identity. While the development and the cellular diversity of the six-layered neocortex are increasingly understood, the olfactory cortex remains poorly documented in these aspects. Here is a review of current knowledge of the development and organization of the olfactory cortex, keeping the analogy with those of the neocortex. The comparison of olfactory cortex and neocortex will allow the opening of evolutionary perspectives on cortical development.
Topics: Animals; Biological Evolution; Cell Movement; Neocortex; Olfactory Cortex
PubMed: 28144624
DOI: 10.1523/ENEURO.0193-16.2016 -
Nature Communications Oct 2023The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing...
The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.
Topics: Mice; Animals; Islands of Calleja; Depression; Ventral Striatum; Olfactory Tubercle; Dopaminergic Neurons
PubMed: 37898623
DOI: 10.1038/s41467-023-42662-z -
Brain and Behavior May 2021Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous...
INTRODUCTION
Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous studies showed that olfactory decline in elderly subjects was associated with volume reductions in the left hippocampus and left parahippocampus without cognitive impairment. The aim of this study is to investigate the link between olfaction and volume reductions in the medial temporal regions including the parahippocampus, entorhinal cortex, and hippocampal subfields.
METHOD
27 elderly subjects and 27 young controls were measured olfaction acuity, cognitive function, and structural magnetic resonance imaging. Image processing and gray matter volumetric segmentation were performed with FreeSurfer. Volume data were analyzed with SPSS Statistics software.
RESULTS
Interesting results of this study were that volume reduction in the entorhinal cortex was not directly linked with declining olfactory ability. Volume reduction in the left entorhinal cortex was correlated with volume reduction in the left parahippocampus and dentate gyrus. However, left parahippocampus volume reduction had the greatest impact on olfactory decline, and the entorhinal cortex and dentate gyrus might additionally contribute to olfactory decline.
CONCLUSION
Our results indicate that olfactory decline may be directly reflected in the medial temporal regions as reduced parahippocampus volumes, rather than as morphological changes in the entorhinal cortex and hippocampus. The parahippocampus may play an important role in the association between memory retrieval and olfactory identification.
Topics: Aged; Entorhinal Cortex; Hippocampus; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Smell
PubMed: 33769719
DOI: 10.1002/brb3.2115