Higher Brain Centers Research Articles

Peripheral preprocessing in Drosophila facilitates odor classification

The mammalian brain implements sophisticated sensory processing algorithms along multilayered ("deep") neural networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. Using Drosophila as a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory receptor neurons. Each compartment operates as a ratiometric unit for specific odor-mixtures. This computation arises from a simple mechanism: electrical coupling between two differently sized neurons. We demonstrate that downstream synaptic connectivity is shaped to optimally leverage amplification of a hedonic value signal in the periphery. Furthermore, peripheral preprocessing is shown to markedly improve novel odor classification in a higher brain center. Together, our work highlights a far-reaching functional role of the sensory periphery for downstream processing. By elucidating the implementation of powerful computations by a shallow network, we provide insights into general principles of efficient sensory processing algorithms.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n=16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n=18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Comfort Therapy with Companionship Improves Learning Memory and Reduces Hyperalgesia in Sickle Mice

Chronic and unpredictable acute pain coexist with cognitive dysfunction in sickle cell disease (SCD). Managing chronic pain is crucial, though efforts are complicated by both physiological and affective contributors to pain. The affective state, which is severely impacted by the environment including stigma and social isolation, plays a substantial role in pain perception and may further exacerbate psychological factors. Therefore, we examined if companionship and social isolation influence cognitive function and pain in SCD. In the present study, we examined the effects of social isolation on hyperalgesia, learning memory, and anxiety in humanized transgenic homozygous BERK mouse model of SCD. At ~3.5 months of age, BERK male mice were paired with age-matched female BERK companions (1 male + 1 female/cage; called companion group) and another group of BERK males were placed into isolation (one male/cage; called isolation group) for ~14 months. Isolation and companion groups were maintained in general housing conditions in the same room. Both groups were assessed for body weight, hyperalgesia and cognitive behaviors. Mechanical hyperalgesia was assessed by counting paw withdrawal frequency (PWF) following 10 applications of a 1.0 g von Frey monofilament (Semmes Weinstein, Stoelting, Wood Dale, IL, USA) to the plantar surface of the hind paw. Cold hyperalgesia was assessed following placement of mice onto a 4°C cold plate chamber (Stoelting) and by measuring PWF over a 2-minute period. Musculoskeletal hyperalgesia was measured by testing grip force of each mouse's peak forepaw grip to a computerized grip force meter (SA Maier, Milwaukee, WI, USA) and normalizing by body weight. The cognitive behavioral assessment consisted of an open field test to assess anxiety-related behaviors, which measured time spent and number of crosses through a central region. Working memory was assessed using novel object recognition and novel placement recognition tests to measure discrimination of novel objects and location. Data are shown as mean ± SEM and comparisons between companionship and isolation groups were performed using unpaired, two-tailed T-tests to determine statistical significance (P<0.05) We observed a significant increase in the body weights of males housed with females ( Companion group) compared to males in isolation (p<0.05). It is likely that males living with a companion were eating more compared to those under isolation. Isolated male sickle mice experience greater hyperalgesia than male mice housed with a female companion. Isolation induces greater PWF to mechanical (P<0.05) and cold (P<0.005) stimuli, indicating exacerbated hypersensitivity to mechanical and cold stimuli. Spontaneous, non-evoked musculoskeletal hyperalgesia was not significantly altered by isolation (P>0.05). Isolation also appeared to impact working and learning memory. Novel object recognition and novel object placement tests revealed reduced discrimination ratios in isolated mice (~25%, P<0.05 and ~25%, P<0.05), which are suggestive of impaired learning and memory function compared to mice with companionship. Open field test showed no significant difference (P>0.05) between isolation and companionship groups in time spent and number of crosses in the open field center area, indicating no detectable differences in anxiety-like behaviors. According to cognitive tests, mice in companionship showed greater novel object and place detection and greater cognitive ability compared to those in isolation. For the first time we show the causal role of social isolation on hyperalgesia and memory in a humanized mouse model of SCD. “ Comfort therapy” with companionship can ameliorate the perception of pain through the higher brain centres. It is also likely that mice in companionship eat more as evinced by a significant increase in their weight, which may provide additional comfort and meet the increased nutritional/calorie demands of SCD due to altered metabolism. Our observations suggest that “ comfort therapy” with improved living conditions and reducing isolation and loneliness may improve pain-related outcomes in SCD.

Child and adolescent obesity

The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joined-up policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.

Different methods for management of gaging reflex during prosthetic treatment

Introduction The reflex of gaging and vomiting is an unpleasant feeling. Its purpose is to protect the upper respiratory tract and to remove foreign particles from posterior part of the oropharynx and upper gastrointestinal tract. Gag reflex could also be provoked by psychogenic stimuli modulated by higher brain centers. A common problem in clinical dental practice are patients with hypersensitivity in the oral cavity. Dental care could be a challenge for the dentists. Detailed anamnesis, clinical examination and gaging reflex management contribute to the appropriate approach in oral rehabilitation. Aim The aim of this study is to present different techniques for gaging and vomiting reflex management during prosthetic treatment Materials and Methods Detailed research in electronic databases Google scholar, Scopus, Pubmed and Research gate was conducted from September 2022 until December 2022. The keywords were: gag reflex, management, dentistry, removable partial denture. The literature was in English. Results A total of 542 articles were found during the literature review. In this study 39 original scientific papers meeting the criteria were included. Data and evidence for the importance of gaging reflex management were found in the reviewed articles. Conclusion The gag reflex decreases the effectiveness of the prosthetic treatment. A number of methods for its management are described in the literature and in the practice. The application of some of them is limited by local or general contraindications. Others could be used after an additional training. Regardless of the methods that are chosen, the dentist must take into account the characteristics of each patient and apply an individual approach.

Colour vision: From sensation to science (in Norwegian)

Throughout history there have been different approaches to pursuing a better understanding of colour and colour vision, depending on the phenomena one wanted to explain. For instance, although seemingly irreconcilable, the opponent-colour theory of Hering (with its yellow-blue and red-green chromatic pairs) and the three-colour theory of Young-Helmholtz (with red, green, and violet as mixture primaries) did in fact illuminate different aspects of colour vision. Thomas Young and Hermann von Helmholtz set out to explain the qualities of colours, but with the help of James C. Maxwell this theory eventually became a three-receptor theory describing additive colour mixtures and colour matches. The three-receptor theory is the foundation of trichromatic colour measurements and a thriving colour technology. Ewald Hering, who also had colour perception as his main concern, appears to have recognized the distinction between receptor excitations and perception. He postulated opponent physiological processes as basis for the two pairs of chromatic colours. Today these theories are combined in an attempt to understand how colour is processed in the higher brain centres.

Olfactory responses of Drosophila are encoded in the organization of projection neurons.

The projection neurons (PNs), reconstructed from electron microscope (EM) images of the Drosophila olfactory system, offer a detailed view of neuronal anatomy, providing glimpses into information flow in the brain. About 150 uPNs constituting 58 glomeruli in the antennal lobe (AL) are bundled together in the axonal extension, routing the olfactory signal received at AL to mushroom body (MB) calyx and lateral horn (LH). Here we quantify the neuronal organization in terms of the inter-PN distances and examine its relationship with the odor types sensed by Drosophila. The homotypic uPNs that constitute glomeruli are tightly bundled and stereotyped in position throughout the neuropils, even though the glomerular PN organization in AL is no longer sustained in the higher brain center. Instead, odor-type dependent clusters consisting of multiple homotypes innervate the MB calyx and LH. Pheromone-encoding and hygro/thermo-sensing homotypes are spatially segregated in MB calyx, whereas two distinct clusters of food-related homotypes are found in LH in addition to the segregation of pheromone-encoding and hygro/thermo-sensing homotypes. We find that there are statistically significant associations between the spatial organization among a group of homotypic uPNs and certain stereotyped olfactory responses. Additionally, the signals from some of the tightly bundled homotypes converge to a specific group of lateral horn neurons (LHNs), which indicates that homotype (or odor type) specific integration of signals occurs at the synaptic interface between PNs and LHNs. Our findings suggest that before neural computation in the inner brain, some of the olfactory information are already encoded in the spatial organization of uPNs, illuminating that a certain degree of labeled-line strategy is at work in the Drosophila olfactory system.

Mechanisms of Arthrogenic Muscle Inhibition.

Arthrogenic muscle inhibition (AMI) continues to be a limiting factor in joint rehabilitation as the inability to volitionally activate muscle significantly dampens recovery. New evidence acquired at higher brain centers and in clinical populations continues to reshape our perspective of what AMI is and how to treat it. This review aims to stimulate discussion about the far-reaching effects of AMI by exploring the interconnected pathways by which it evolves. To discuss how reflexive inhibition can lead to adaptations in brain activity, to illustrate how changes in descending motor pathways limit our ability to contract muscle following injury, and to summarize the emerging literature on the wide-reaching effects of AMI on other interconnected systems. The databases PubMed, SPORTDiscus, and Web of Science were searched for articles pertaining to AMI. Reference lists from appropriate articles were cross-referenced. AMI is a sequential and cumulative neurological process that leads to complex clinical impairments. Originating with altered afferent information arising from an injured joint, patients experience changes in afferent information, reflexive muscle inhibition, deficiencies in somatosensation, neuroplastic compensations in higher brain centers, and ultimately decreased motor output to the muscle surrounding the joint. Other aspects of clinical function, like muscle structure and psychological responses to injury, are also impaired and influenced by AMI. Removing, or reducing, AMI should continue to be a focus of rehabilitation programs to assist in the optimization of health after joint injury.

The Fundamental Basis of Palpitations: A Neurocardiology Approach.

Palpitations are a common symptom that may indicate cardiac arrhythmias, be a somatic complaint in anxiety disorders, and can be present in patients without either condition. The objective of this review was to explore the pathways and fundamental mechanisms through which individuals appreciate palpitations. Cardiac afferents provide beat-to-beat sensory information on the heart to the spinal cord, brain stem, and higher brain centers. Cardioception, a subset of interoception ('the physiological sense of the condition of the body'), refers to sensing of the heartbeat. High cardioception is present in persons with lower body mass index, lower percentages of body fat, and anxiety disorders. Low cardioception (lower interoceptive awareness) is associated with psychiatric disorders, such as depression, personality disorders, and schizophrenia. CNS sites associated with heartbeat detection have been identified by functional magnetic resonance imaging studies and heartbeat-evoked electroencephalogram potentials. The right insula, cingulate gyrus, somatomotor and somatosensory cortices nucleus accumbens, left subthalamic nucleus, and left ventral capsule/striatum are implicated in both palpitations and heartbeat detection. Involvement of the brain as a primary modulator of palpitations rests on the data that various areas of the brain are activated in association with cardioception, the ability of focal brain stimulation to induce palpitations, the ability of central alpha receptor agonists and antagonists to modulate palpitations, and suppression of palpitations by transcranial repetitive magnetic stimulation (rTMS). Palpitations should be viewed as a pathway extending from the heart to the brain. Palpitations are, in part, a reflection of an individual's cardioception awareness, which is modulated by body size, percentage of body fat, and psychological or psychiatric conditions. Palpitations can originate in the brain and involve central neurotransmitters. Treatment of palpitations unrelated to cardiac arrhythmias or anxiety disorders should consider the use of central alpha-2 agonists and possibly rTMS.

Understanding dreams -the comprehensive, interdisciplinary way: A review

Dreams are virtual repetitions during sleep, of what we perceive and act, in reality, when we are awake. The basis of wakeful state, is due to the sensory inputs from the sensory organs (through the ascending tracts) and the motor output from the respective brain centres (through the descending tracks), as well as, due to the activated ascending reticular activating system. (ARAS) and the posterior hypothalamus. In the dream state, both these sensory inputs and motor outputs are suspended and the ARAS is deactivated. Even the brain's electrical networks ie the Salience and the Default network,(DMN) are different, during working and sleeping States, respectively. Yet one can see the images of persons and places etc, in the dreams. It follows, that the dreams could be, the unconscious recollection and replay of the past experiences during the sleep. Thus, the dreams are linked to the memory formation, consolidation and it's retrieval. Truly, the parts of the brain involved in dreams, are the same as those involved in the consolidation, storage and retrieval of the memory, (Hippocampus) and emotions (Amygdala) and the attempted meaningful interpretation, in the form of a storyline, by the higher brain centers, in the neocortex (like medial prefrontal cortex, etc). In fact, the hippocampus has been shown to utilize the memory, to construct novel, imagined scenarios and simulate possible future events. An area, just above the nape of neck called the “posterior cortical hot zone", is considered to be the “factory of dreams “.The electrical waves (like the Hippocampal theta waves and pontine -geniculate -occipital waves) and the neurotransmitters, (like cholinergic, glutamatergic, adrenergic, serotonergic and GABAergic ) link the respective centres involved in the dream process. Several theories (like Freud's, Carl Jung',s, activation- synthesis theory etc),are put forward, as well as, several approaches (like Psychodynamic, behavioral and Neuroscience approaches) are followed.The multiplicity of, the theories and approaches, is a testimony to the fact that none of them, has the whole truth. A comprehensive interdisciplinary approach is attempted in this article, by reviewing the various facets of the dreams, like the neuroanatomy of the structures involved, their interconnections, the electro -physiology of the brain, the physiological changes that occur during REM sleep (during which the dreams occur), the clinical entities that mimic the dream- state but are distinct, like, Imagination, Imagery, Recall and the Hallucinations, including, the sleep hallucinations (hypnagogic and Hypnopompic), forebrain Analysis and the forebrain synthesis ete, and sleep disorders (like sleep paralysis, sleep myoclonus) etc., in search of clues, for the better understanding of the subject of dreams.

Novelty detection in early olfactory processing of the honey bee, Apis mellifera.

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain–the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both tentative projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may represent familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers.

Біль у спині як часта причина звернення до невролога. Етіологія, патофізіологія і лікування болю

Біль — одна з найбільш поширених причин звернення до невролога. Приблизно 80 % населення періодично страждає від болю в спині, особливо від болю в попереку. Нервова система реагує на широкий спектр ендогенних і екзогенних подразників. Біль забезпечується за допомогою ноцицепторів, через периферичні сенсорні нейрони, які сигналізують про потенційне пошкодження шкіри за допомогою перетворення стимулів в електричні сигнали, які, у свою чергу, надходять до вищих мозкових центрів.

The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx.

To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells (KCs) of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral (APL) neuron in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic KCs. Combining electron microscopy (EM) data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the KCs requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.

Modulation of recombinant human alpha 1 glycine receptor by flavonoids and gingerols.

The inhibitory glycine receptor (GlyR) is a principal mediator of fast synaptic inhibition in mammalian spinal cord, brainstem, and higher brain centres. Flavonoids are secondary plant metabolites that exhibit many beneficial physiological effects, including modulatory action on neuronal receptors. Using whole-cell current recordings from recombinant human α1 GlyRs, expressed in HEK293cells, we compared the flavonols kaempferol and quercetin, the flavanone naringenin, the flavones apigenin and nobiletin, the isoflavone genistein, and two gingerols, 6-gingerol and 8-gingerol for their modulation of receptor currents. All compounds were inhibitors of the GlyR with IC50 values ranging between 9.3±2.6µM (kaempferol) and 46.7±6.5µM (genistein), following a mixed mode of inhibition. Co-application of two inhibitors revealed distinct binding sites for flavonoids and gingerols. Pore-lining mutants T258A and T258S were strongly inhibited by quercetin and naringenin, but not by 6-gingerol, confirming the existence of distinct binding sites for flavonoids and gingerols. Apigenin, kaempferol, nobiletin, naringenin and 6-gingerol showed biphasic action, potentiating glycine-induced currents at low concentration of both, modulator and glycine, and inhibiting at higher concentrations. Identification of distinct modulatory sites for flavonoids and related compounds may present pharmacological target sites and aid the discovery of novel glycinergic drugs.

Sympathetic reactivity and inflammation: another joint problem in rheumatoid arthritis?

Sympathetic reactivity and inflammation: another joint problem in rheumatoid arthritis?

Pain pathways and potential new targets for pain relief

Pain is an unpleasant sensory and emotional experience that affects a sizable percentage of people on a daily basis. Sensory neurons known as nociceptors built specifically to detect damaging stimuli can be found throughout the body. They transmit information about noxious stimuli from mechanical, thermal, and chemical sources to the central nervous system and higher brain centers via electrical signals. Nociceptors express various channels and receptors such as voltage-gated sodium and calcium channels, transient receptor potential channels, and opioid receptors that allow them to respond in a highly specific manner to noxious stimuli. Attenuating the pain response can be achieved by inhibiting or altering the expression of these pain targets. Achieving a deeper understanding of how these receptors can be affected at the molecular level can lead to the development of novel pain therapies. This review will discuss the mechanisms of pain, introduce the various receptors that are responsible for detecting pain, and future directions in pharmacological therapies.

Mechanisms underlying the sensation of dyspnea.

Dyspnea is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. It is a common symptom among patients with respiratory diseases that reduces daily activities, induces deconditioning, and is self-perpetuating. Although clinical interventions are needed to reduce dyspnea, its underlying mechanism is poorly understood depending on the intertwined peripheral and central neural mechanisms as well as emotional factors. Nonetheless, experimental and clinical observations suggest that dyspnea results from dissociation or a mismatch between the intended respiratory motor output set caused by the respiratory neuronal network in the lower brainstem and the ventilatory output accomplished. The brain regions responsible for detecting the mismatch between the two are not established. The mechanism underlying the transmission of neural signals for dyspnea to higher sensory brain centers is not known. Further, information from central and peripheral chemoreceptors that control the milieu of body fluids is summated at higher brain centers, which modify dyspneic sensations. The mental status also affects the sensitivity to and the threshold of dyspnea perception. The currently used methods for relieving dyspnea are not necessarily fully effective. The search for more effective therapy requires further insights into the pathophysiology of dyspnea.

Increased number of activated microglia in rat spinal cord during early stage of diabetic induction.

Diabetic neuropathy is a common chronic complication in diabetes mellitus. Such neuropathy associates with chronic inflammation and immune system activation. Microglia, a type of neuroglia, are involved in the immune system and are found in grey and white matter of the central nervous system, such as the brain and spinal cord. The spinal cord connects the peripheral nervous system and the higher brain centre. Hyperglycaemia during diabetes mellitus has been found to activate and increase number of microglia in the dorsal grey horn or column of the lumbar segments in spinal cord, which release several cytokines in the development of hypersensitivity in diabetic neuropathic pain. Therefore, in this study, anatomical alterations of rat spinal microglia in all areas (dorsal, intermediate and ventral columns of grey matter and dorsal, lateral and ventral funiculi of white matter) in cervical enlargement, thoracic level and lumbosacral enlargement were observed in early stage of diabetic conditions by using light and transmission electron microscopies. The numbers of microglia in all parts of grey and white matter of all spinal levels significantly increased in the diabetic group. The structures and ultrastructures of microglia in grey and white matter at cervical enlargement, thoracic level and lumbosacral enlargement similarly changed in diabetes. In diabetic rats, microglia became hypertrophied with a pale nucleus. Moreover, short fragments of rough endoplasmic reticulum, elevated numbers of lysosomes and numerous actin filaments in the cytoplasm were examined. Microglial phagocytosis of myelin and axonal debris were also observed. In this investigation, the morphology of spinal microglia during short-term diabetes became activated during hyperglycaemia. It is suggested that these changes may be involved in the development of diabetic neuropathic pain in the spinal cord.

Whole-Brain Calcium Imaging in Larval Xenopus.

Sensory systems detect environmental stimuli and transform them into electrical activity patterns interpretable by the central nervous system. En route to higher brain centers, the initial sensory input is successively transformed by interposed secondary processing centers. Mapping the neuronal activity patterns at all of those stages is essential to understand sensory information processing. Larval Xenopus laevis is very well-suited for whole-brain imaging of neuronal activity. This is mainly due to its small size, transparency, and the accessibility of both peripheral and central parts of sensory systems. Here we describe a protocol for calcium imaging at several levels of the olfactory system using focal injection of chemical calcium indicator dyes or a Xenopus transgenic line with neuronal GCaMP6s expression. In combination with fast volumetric multiphoton microscopy, the calcium imaging methods described can provide detailed insight into spatiotemporal activity of entire brain regions at different stages of sensory information processing. Although the methods are broadly applicable to the central nervous system, in this work we focus on protocols for calcium imaging of glomeruli in the olfactory bulb and odor-responsive neurons in the olfactory amygdala.

The effect of stroke on micturition associated brain activity: A pilot fMRI study.

Cerebral stroke is a unique model for studying the role of the brain in lower urinary tract (LUT) control. By its nature, stroke must change the activity of the brain to cause LUT dysfunction. The objective of this study was to describe changes in micturition-related brain activity in patients who develop LUT symptoms (LUTS) after a cerebral stroke. Healthy controls (HC, n = 10) and patients who developed storage LUTS after a cerebral stroke (n = 7) were recruited. Functional magnetic resonance imaging was used to assess brain activity in each subject. In the task-based block design, blood-oxygen-level-dependent (BOLD) signal was detected during rest, active bladder filling, and bladder voiding. BOLD signal intensity was compared between HCs and stroke subjects during bladder filling, voiding, and voiding initiation. Stroke subjects exhibited higher activity in the periaqueductal gray and cerebellum during bladder filling and bladder voiding. HCs exhibited more intense activity in higher centers, such as the cingulate cortex, motor cortex, and the dorsolateral prefrontal cortex in each of the phases examined. Subjects with stroke-related LUTS exhibit a specific pattern of brain activity during bladder filling and voiding. There appears to be a greater reliance on primitive centers (cerebellum, midbrain) than in healthy controls during both phases of the micturition cycle. We hypothesize that these findings may reflect loss of connectivity with higher brain centers after a stroke.