Abstract Olfaction, despite being evolutionarily one of the oldest senses, is complex in structure and function. It can distinguish between trillions of odorants, provides orientation, mediates social interactions, and serves as a warning system. Sensory signals from the periphery are first processed in the olfactory bulb (OB) and then distributed to several olfactory cortical structures. Unlike other sensory modalities, this primary sensory information is not relayed via the thalamus. One prominent olfactory cortical region is the anterior olfactory nucleus (AON), a two-layered structure located within the olfactory peduncle. The AON exerts strong reciprocal connections not only to the OB but also to higher brain areas, e.g., the piriform cortex (PCx), thereby serving as a hub for bottom-up and top-down information processing. However, the functional role of the AON is not well-understood. Here, we provide an overview of recent publications investigating the function of AON in olfactory processing and behavior and present a framework for future research on this fascinating archicortical structure.
Abstract The olfactory epithelium (OE) and its associated perireceptor space, i.e., the mucus layer (ML) covering the epithelium, are the most peripheral parts of the vertebrate olfactory system. The olfactory receptor neurons (ORNs), one of the cell types of the OE, are the odorant detectors of the olfactory system. These bipolar neurons extend their apical appendages, which express odorant receptors, into the ML. The binding of odorants to odorant receptors is the initial step of odor processing. The vast majority of research on the peripheral olfactory system has focused on the ORNs and the molecular components of the olfactory transduction cascades. Less attention has been directed to the other cell types of the OE and their physiological functions. For a long time, it was assumed that the olfactory signals detected in the OE are transmitted to the olfactory bulb without preprocessing, but this view turned out to be over-simplistic. It has been shown that the olfactory signals are critically modulated already in the OE. Despite compelling evidence, many descriptions of the olfactory system still ignore the existence of these peripheral modulatory mechanisms. The importance of peripheral modulation of the olfactory signals, the physiological functions of the other epithelial cell types, the extrinsic innervation of the olfactory mucosa, and the perireceptor space are only slowly coming into focus in the olfactory research. Furthermore, several intraepithelial signaling pathways that signal epithelial damage and initiate regenerative processes have recently been discovered. This review provides a concise overview of the current knowledge of peripheral events in the olfactory mucosa and the perireceptor space.
Abstract Brain circuits involved in pain chronicity shift from areas involved in nociceptive processing to those associated with emotional and motivational processes. They overlap with circuits relevant for anxiety, fear and depression and are characterized by deficient prefrontal control mechanisms. Noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation, transcranial direct and alternating current stimulation directly impact on these circuits and pain. Neurofeedback and brain-computer interfaces as well as various types of cognitive and behavioral interventions also alter these circuits. The analysis of brain changes related to pain chronicity helps to mechanistically tailor interventions to patient characteristics, can increase treatment efficacy and efficiency and can identify new treatment approaches.
Abstract Several forms of chronic pain do not respond to the conventional analgesics, such as opioids, but can be treated with antidepressants, such as serotonin and noradrenalin reuptake inhibitors (SNRIs). Recent studies indicate that noradrenalin signalling is a key target for SNRI-induced analgesia in neuropathic pain. SNRIs inhibit chronic pain by blocking reuptake of noradrenalin and subsequent activation of adrenergic receptors on neurons in the dorsal horn of the spinal cord. However, in the nervous system, various subtypes of adrenergic receptors are highly expressed by astrocytes and microglial cells. Activation of these receptors on astrocytes engages complex intracellular signalling pathways and prevents inflammatory changes of microglia, which in turn can affect neuronal activity. Hence, SNRIs-induced modulations of the glial cell physiology can impact neural circuit functions and pain perception. In this review, we summarize our current knowledge on the impact of SNRIs on glial cells and in modulating chronic pain in experimental animal models.
Abstract Interactions of the immune system and the nociceptive system play an important role in the generation and maintenance of pain in musculoskeletal diseases and in disease development. In inflamed tissue peripheral nociceptive neurons are rendered hyperexcitable by proinflammatory cytokines, antigen/antibody complexes and other immune mediators. Spinal nociceptive neurons are rendered hyperexcitable with the support of microglial cells, the immune cells of the central nervous system. The so-elicited sensitization of pain pathways has a strong impact on pain processing in the brain. On the other hand, immune processes are regulated by the nervous system. Sensory neurons, by releasing neuropeptides, and efferent neurons of the sympathetic nervous system support immune processes which promote disease development.
Abstract Sensory input across modalities is highly dynamic, continuously confronting the brain with the task of making sense of the external world. Olfaction is a key sense that many species depend on for survival, for example to locate food sources and mating partners or to avoid encountering predators. In the absence of visual cues, olfactory cues are especially useful, as they provide information over a large range of distances. Natural odours form temporally complex plumes that show rapid fluctuations in odour concentration carrying information about the location of an odour source. This review focuses on how primarily mammals use this spatial information from olfactory cues to navigate their environment. I highlight progress made on the physical description of dynamically fluctuating odours, behavioural paradigms to investigate odour-guided navigation and review initial findings on the underlying neural mechanisms that allow mammals to extract spatial information from the dynamic odour landscape.
Abstract In this review, we aim to integrate our recent findings on the vasopressin system and its role in social discrimination with other known neuromodulatory mechanisms in the olfactory bulb that are involved in different experimental models of social memory. Behavioral paradigms commonly used to investigate odor-related social memory are individual social memory in rodents, lamb recognition in sheep, and the Bruce effect in female mice. All three cases involve neuromodulation in the main and/or the accessory olfactory bulb, the first centers for olfactory processing. As a large diversity of neuromodulators participate in social memory formation, here, we focus primarily on shared neuromodulatory systems and their physiological effects, in particular, the social neuropeptides, vasopressin and oxytocin, and the arousal-related modulators, acetylcholine and noradrenaline.
Abstract According to best current estimates, approximately 10% of those infected with SARS-CoV-2-virus experience long-term clinical and nonspecific neurological symptoms that may last for several weeks or months. This is currently referred to as “Long-COVID” or “Post-COVID-Syndrome”. Based on current knowledge, the most common long-term symptoms of COVID-19 disease include fatigue and poor concentration, but particularly also headache and musculoskeletal pain. However, given the novelty of COVID-19, only a few studies have systematically evaluated the central nervous alterations in the pain processing structures of our brain. Those first insights are yet important in order to offer patients adequate therapeutic options. Based on a systematic review of the literature, we will therefore provide an overview of the central nervous alterations in the brain described in the context of SARS-CoV-2 infection, focusing on findings with brain imaging.
On January 25, 2022, Professor Hans-Joachim Pflüger passed away. Hans-Joachim Pflüger conducted research in the field of neuroethology, with a focus on the development, anatomy, and function of sensorimotor networks underlying insect locomotion. As founding member and one of the presidents of the German Neuroscience Society, Hans-Joachim Pflüger was a driving force behind the development of the Neurosciences in Germany and Europe. This obituary reflects on his curriculum vitae. It shall honor his scientific and professional achievements, and importantly, also his wonderful personality, which makes this loss so sad across the manifold levels of his life and his legacy, the family, the professional and the scientific community.
Abstract Familial adult myoclonic epilepsy (FAME) is a rare autosomal dominant disorder characterized by cortical myoclonic tremor and seizures. FAME has been mapped to chromosomes (chr) 2, 3, 5 and 8, but the cause has remained elusive for more than a decade. An expansion of intronic TTTTA and TTTCA repeats in SAMD12 was identified as the cause of FAME1 in Japanese families linked to chr 8 in 2018. This discovery triggered the identification of identical repeat expansions at five additional loci (FAME2: STARD7; FAME3: MARCHF6; FAME4: YEATS2; FAME6: TNRC6A and FAME7: RAPGEF2). These genes encode proteins with different functions and subcellular localizations and their expression is unaltered in available peripheral tissues, suggesting that the expansion is pathogenic independently of the gene itself. The pathophysiological mechanisms are not yet known but possibly include toxicity at the RNA level or translation of toxic polypeptides from the repeats, a mechanism known as repeat-associated non-AUG (RAN) translation. FAME is a paradigm of human genetic disorder caused by a non-coding expansion unrelated to the gene where it occurs.
Abstract Olfaction, despite being evolutionarily one of the oldest senses, is complex in structure and function. It can distinguish between trillions of odorants, provides orientation, mediates social interactions, and serves as a warning system. Sensory signals from the periphery are first processed in the olfactory bulb (OB) and then distributed to several olfactory cortical structures. Unlike other sensory modalities, this primary sensory information is not relayed via the thalamus. One prominent olfactory cortical region is the anterior olfactory nucleus (AON), a two-layered structure located within the olfactory peduncle. The AON exerts strong reciprocal connections not only to the OB but also to higher brain areas, e.g., the piriform cortex (PCx), thereby serving as a hub for bottom-up and top-down information processing. However, the functional role of the AON is not well-understood. Here, we provide an overview of recent publications investigating the function of AON in olfactory processing and behavior and present a framework for future research on this fascinating archicortical structure.
Article Newly DFG-funded research training group at the University of Kassel: “Biological clocks on multiple time scales” GRK 2749/1 was published on November 1, 2022 in the journal Neuroforum (volume 28, issue 4).
Abstract “Blindness separates from things; deafness separates from people.” This quote attributed to the deaf-blind author and activist Helen Keller (1880–1968) indicates the importance of proper hearing for social interaction in our society which is largely driven by acoustic communication. A major cause for auditory dysfunction lies in our genome with currently more than 100 genes linked to hearing loss. One example is the microRNA gene Mir-96 of the microRNA-183 family. MicroRNAs are small regulatory RNAs involved in the finetuning of gene expression. Analyses of transgenic mouse models established this microRNA family as a major regulator for the function of the inner ear as well as synaptic transmission in the auditory brainstem. The microRNA-183 family might therefore play an important role in coordinating the development of the peripheral and central auditory system and their specializations.
