Differential serotonergic modulation of principal neurons and interneurons in the anterior piriform cortex

Originating from the brainstem raphe nuclei, serotonin is an important neuromodulator involved in a variety of physiological and pathological functions. Specific optogenetic stimulation of serotonergic neurons results in the divisive suppression of spontaneous, but not sensory evoked activity in the majority of neurons in the primary olfactory cortex and an increase in firing in a minority of neurons. To reveal the mechanisms involved in this dual serotonergic control of cortical activity we used a combination of in vitro electrophysiological recordings from identified neurons in the primary olfactory cortex, optogenetics and pharmacology and found that serotonin suppressed the activity of principal neurons, but excited local interneurons. The results have important implications in sensory information processing and other functions of the olfactory cortex and related brain areas.

Parallel processing by distinct classes of principal neurons in the olfactory cortex

Understanding how distinct neuron types in a neural circuit process and propagate information is essential for understanding what the circuit does and how it does it. The olfactory (piriform, PCx) cortex contains two main types of principal neurons, semilunar (SL) and superficial pyramidal (PYR) cells. SLs and PYRs have distinct morphologies, local connectivity, biophysical properties, and downstream projection targets. Odor processing in PCx is thought to occur in two sequential stages. First, SLs receive and integrate olfactory bulb input and then PYRs receive, transform, and transmit SL input. To test this model, we recorded from populations of optogenetically identified SLs and PYRs in awake, head-fixed mice. Notably, silencing SLs did not alter PYR odor responses, and SLs and PYRs exhibited differences in odor tuning properties and response discriminability that were consistent with their distinct embeddings within a sensory-associative cortex. Our results therefore suggest that SLs and PYRs form parallel channels for differentially processing odor information in and through PCx.

Disorders of the Cranial Nerves and Brainstem

This chapter briefly repeats key anatomic characteristics and then reviews clinical disorders affecting each cranial nerve in addition to the brainstem. More specifically, this chapter covers cranial nerves I, V, VII, and IX through XII plus the brainstem. The olfactory nerve is a special visceral afferent nerve that functions in the sense of smell. The axons of the olfactory receptor cells within the nasal cavity extend through the cribriform plate to the olfactory bulb. These olfactory receptor cell axons synapse with mitral cells in the olfactory bulb. Mitral cell axons project to the primary olfactory cortex and amygdala. The olfactory cortex interconnects with various autonomic and visceral centers.

Diffusion Tensor Imaging of the Olfactory System in Older Adults With and Without Hyposmia

Objectives: To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia.Methods: Data from the Brief Smell Identification Test (BSIT) were obtained in 1998–99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT: 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006–08 [Interval of time: mean (SD): 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011–12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011–12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype.Results: Hyposmia in 1998–99 (n = 57, 21.59%) was significantly associated with greater MD in 2006–08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value): 0.414 (0.01); 0.527 (0.01); respectively].Conclusion: Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.

Effective connectivity reveals distinctive patterns in response to others' genuine affective experience of disgust as compared to pain

Empathy is significantly influenced by the identification of others' emotions. In a recent study, we have found increased activation in the anterior insular cortex (aIns) that could be attributed to affect sharing rather than perceptual saliency, when seeing another person genuinely experiencing pain as opposed to merely acting to be in pain. This study further revealed effective connectivity between aIns and the right supramarginal gyrus (rSMG) to track what another person really feels. In the present study, we used a similar paradigm to investigate the corresponding neural signatures in the domain of empathy for disgust - with participants seeing others genuinely sniffing unpleasant odors as compared to pretending to smell something disgusting. Consistent with the previous findings on pain, we found stronger activations in aIns associated with affect sharing for genuine disgust compared with pretended disgust. However, instead of rSMG we found engagement of the olfactory cortex. Using dynamic causal modeling (DCM), we estimated the neural dynamics of aIns and the olfactory cortex between the genuine and pretended conditions. This revealed an increased excitatory modulatory effect for genuine disgust compared to pretended disgust. For genuine disgust only, brain-to-behavior regression analyses highlighted a link between the observed modulatory effect and the perspective-taking empathic trait. Altogether, the current findings complement and expand our previous work, by showing that perceptual saliency alone does not explain responses in the insular cortex. Moreover, it reveals that different brain networks are implicated in a modality-specific way when sharing the affective experiences associated with pain vs. disgust.

Unilaterally Disrupted Structural and Functional Connectivity of The Fronto-Iimbic System In Idiopathic Hypogonadotropic Hypogonadism

Background: Idiopathic hypogonadotropic hypogonadism (IHH) is rare and can either be associated with normal or defective olfactory sensation, classified as normosmic IHH (nIHH) or Kallmann’s syndrome (KS), respectively. We do not yet understand the central processing pathways in the olfactory system, especially regarding these disorders. We aimed to compare the resting-state structural and functional connectivity (FC) of olfactory neural pathways in patients with nIHH and KS.Methods: A total of 50 males were studied: 13 nIHH patients, 12 KS patients, and 25 healthy controls (HCs). All subjects underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scans. Structural and functional connectivity data analyses were then performed.Results: The results indicated that fractional anisotropy (FA) was significantly decreased in the right uncinate fasciculus (UF) in the KS group. The olfactory cortex FC values of the right gyrus rectus and orbitofrontal cortex (OFC) in the KS group were decreased compared with those in the HC group and increased compared with those in the nIHH group (nIHH< KS <HC). Moreover, there were significant negative correlations between right UF FA and olfactory cortex FC to both the gyrus rectus and OFC within the nIHH and HC groups.Conclusion: We have reported significant structural and functional disruptions unilaterally at the right junction of the fronto-limbic system in KS patients. The results may indicate that a specific structural-functional asymmetry exists in the olfactory cortex pathways in KS patients.

Top-down feedback enables flexible coding strategies in olfactory cortex

In chemical sensation, multiple models have been proposed to explain how odors are represented by patterns of neuronal activity in the olfactory cortex. One hypothesis is that the identity of combinations of active neurons within specific sniff-related time windows are critical for encoding information about odors. Another model is that patterns of neural activity evolve across time and it is this temporal structure that is essential for encoding odor information. Interestingly, we found that top-down feedback to the olfactory bulb dictates what information is transmitted to the olfactory cortex by switching between these two strategies. Using a detailed model of the early olfactory system, we demonstrate that feedback control of inhibitory granule cells in the main olfactory bulb influences the balance between excitatory and inhibitory synaptic currents in mitral cells, thereby restructuring the firing patterns of piriform cortical cells across time. This resulted in performance gains in both the accuracy and reaction time of odor discrimination tasks. These findings lead us to propose a new framework for early olfactory computation, one in which top-down feedback to the bulb flexibly controls the temporal structure of neural activity in olfactory cortex, allowing the early olfactory system to dynamically switch between two distinct models of coding.

Parallel processing by distinct classes of principal neurons in the olfactory cortex

Understanding the specific roles that different neuron types play within a neural circuit is essential for understanding what that circuit does and how it does it. The primary olfactory (piriform, PCx) cortex contains two main types of principal neurons: semilunar (SL) and pyramidal (PYR). SLs and PYRs have different morphologies, connectivity, biophysical properties, and downstream projections, predicting distinct roles in cortical odor processing. The prevailing model is that odor processing in PCx occurs in two stages, where SLs are the primary recipients of olfactory bulb (OB) input, and PYRs receive and transform information from SLs. Here we recorded from optogenetically-identified SLs and PYRs in awake, head-fixed mice. We found differences in SL and PYR odor-evoked activity that reflect their different connectivity profiles. But SL responses did not precede PYR responses and suppressing SL activity had little effect on PYR odor responses. These results suggest that SLs and PYRs form parallel odor processing channels.

Tai Chi Chuan Alters Brain Functional Network Plasticity and Promotes Cognitive Flexibility

Objective: This study used resting-state functional magnetic resonance imaging to investigate the effects of 8 weeks of Tai Chi Chuan and general aerobic exercise on the topological parameters of brain functional networks, explored the advantages of Tai Chi Chuan for improving functional network plasticity and cognitive flexibility, and examined how changes in topological attributes of brain functional networks relate to cognitive flexibility.Methods: Thirty-six healthy adults were grouped into Tai Chi Chuan (Bafa Wubu of Tai Chi), general aerobic exercise (brisk walking), and control groups. All of the subjects underwent fMRI and behavioral assessment before and after the exercise intervention.Results: Tai Chi Chuan exercise significantly enhanced the clustering coefficient and local efficiency compared with general aerobic exercise. Regarding the nodal properties, Tai Chi Chuan significantly enhanced the nodal clustering coefficient of the bilateral olfactory cortex and left thalamus, significantly reduced the nodal clustering coefficient of the left inferior temporal gyrus, significantly improved the nodal efficiency of the right precuneus and bilateral posterior cingulate gyrus, and significantly improved the nodal local efficiency of the left thalamus and right olfactory cortex. Furthermore, the behavioral performance results demonstrated that cognitive flexibility was enhanced by Tai Chi Chuan. The change in the nodal clustering coefficient in the left thalamus induced by Tai Chi Chuan was a significant predictor of cognitive flexibility.Conclusion: These findings demonstrated that Tai Chi Chuan could promote brain functional specialization. Brain functional specialization enhanced by Tai Chi Chuan exercise was a predictor of greater cognitive flexibility.