Comparing vibrissal morphology and infraorbital foramen area in pinnipeds.

Pinniped vibrissae are well-adapted to sensing in an aquatic environment, by being morphologically diverse and more sensitive than those of terrestrial species. However, it is both challenging and time-consuming to measure vibrissal sensitivity in many species. In terrestrial species, the infraorbital foramen (IOF) area is associated with vibrissal sensitivity and increases with vibrissal number. While pinnipeds are thought to have large IOF areas, this has not yet been systematically measured before. We investigated vibrissal morphology, IOF area, and skull size in 16 species of pinniped and 12 terrestrial Carnivora species. Pinnipeds had significantly larger skulls and IOF areas, longer vibrissae, and fewer vibrissae than the other Carnivora species. IOF area and vibrissal number were correlated in Pinnipeds, just as they are in terrestrial mammals. However, despite pinnipeds having significantly fewer vibrissae than other Carnivora species, their IOF area was not smaller, which might be due to pinnipeds having vibrissae that are innervated more. We propose that investigating normalized IOF area per vibrissa will offer an alternative way to approximate gross individual vibrissal sensitivity in pinnipeds and other mammalian species. Our data show that many species of pinniped, and some species of felids, are likely to have strongly innervated individual vibrissae, since they have high values of normalized IOF area per vibrissa. We suggest that species that hunt moving prey items in the dark will have more sensitive and specialized vibrissae, especially as they have to integrate between individual vibrissal signals to calculate the direction of moving prey during hunting.

California sea lions employ task-specific strategies for active touch sensing.

Active sensing is the process of moving sensors to extract task-specific information. Whisker touch is often referred to as an active sensory system as whiskers are moved with purposeful control. Even though whisker movements are found in many species, it is unknown whether any animal can make task-specific movements with their whiskers. California sea lions (Zalophus californianus) make large, purposeful whisker movements and are capable of performing many whisker-related discrimination tasks. Therefore, California sea lions are an ideal species to explore the active nature of whisker touch sensing. Here, we show that California sea lions can make task-specific whisker movements. California sea lions move their whiskers with large amplitudes around object edges to judge size, make smaller, lateral stroking movements to judge texture and make very small whisker movements during a visual task. These findings, combined with the ease of training mammals and measuring whisker movements, makes whiskers an ideal system for studying mammalian perception, cognition and motor control.

Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD: a collaborative multi-modal study.

Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease. Methods: TgF344-AD rats and wild-type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (Aß) and [18F]ASEM (α7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, Aß, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed. Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected Aß accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. Aß plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to Aß plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the Aß plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-acetyl-aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and -31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG). Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD.

Microglial peri-somatic abutments classify two novel types of GABAergic neuron in the inferior colliculus.

Emerging evidence suggests functional roles for microglia in the healthy, mature nervous system. However, we know little of the cellular density and ramified morphology of microglia in sensory systems, and even less of their inter-relationship with inhibitory neurons. We therefore conducted fluorescent multi-channel immunohistochemistry and confocal microscopy in guinea pigs of both sexes for Iba1, GAD67, GFAP, calbindin, and calretinin. We explored these markers in the inferior colliculi (IC), which contain sub-regions specialized for different aspects of auditory processing. First, we found that while the density of Iba1+ somata is similar throughout the IC parenchyma, Iba1+ microglia in dorsal cortex are significantly more ramified than those in the central nucleus or lateral cortex. Conversely, Iba1+ ramifications in ventral central nucleus, a region with the highest density of GAD67+ (putative GABAergic) neurons in IC, are longer with fewer ramifications. Second, we observed extensive abutments of ramified Iba1+ processes onto GAD67+ somata throughout the whole IC and developed novel measures to quantify these. Cluster analyses revealed two novel sub-types of GAD67+ neuron that differ in the quantity of Iba1+ somatic abutments they receive. Unlike previous classification schemes for GAD67+ neurons in IC, these clusters are not related to GAD67+ soma size. Taken together, these data demonstrate that microglial ramifications vary between IC sub-regions in the healthy, adult IC, possibly related to the ongoing demands of their niche. Furthermore, Iba1+ abutments onto neuronal somata are a novel means by which GAD67+ neurons can be classified.

Pinnipeds orient and control their whiskers: a study on Pacific walrus, California sea lion and Harbor seal.

Whisker touch is an active sensory system. Previous studies in Pinnipeds have adopted relatively stationary tasks to judge tactile sensitivity, which may not accurately promote natural whisker movements and behaviours. This study developed a novel feeding task, termed fish sweeping to encourage whisker movements. Head and whisker movements were tracked from video footage in Harbor seal (Phoca vitulina), California sea lion (Zalophus californianus) and Pacific walrus (Odobenus rosmarus divergens). All species oriented their head towards the moving fish target and moved their whiskers during the task. Some species also engaged in whisker control behaviours, including head-turning asymmetry in the Pacific walrus, and contact-induced asymmetry in the Pacific walrus and California sea lion: behaviours that have only previously been observed in terrestrial mammals. This study confirms that Pinnipeds should be thought of as whisker specialists, and that whisker control (movement and positioning) is an important aspect of touch sensing in these animals, especially in sea lions and walruses. That the California sea lion controls whisker movement in relation to an object, and also had large values of whisker amplitude, spread and asymmetry, suggests that California sea lions are a promising model with which to further explore active touch sensing.

Auditory and visual hallucination prevalence in Parkinson's disease and dementia with Lewy bodies: a systematic review and meta-analysis.

BACKGROUND: Non-motor features of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), such as auditory hallucinations (AH), contribute to disease burden but are not well understood. METHODS: Systematic review and random-effects meta-analyses of studies reporting AH associated with PD or DLB. Prevalence of visual hallucinations (VH) in identified studies meeting eligibility criteria were included in meta-analyses, facilitating comparison with AH. Synthesis of qualitative descriptions of AH was performed. PubMed, Web of Science and Scopus databases were searched for primary journal articles, written in English, published from 1970 to 2017. Studies reporting AH prevalence in PD or DLB were screened using PRISMA methods. RESULTS: Searches identified 4542 unique studies for consideration, of which, 26 met inclusion criteria. AH pooled prevalence in PD was estimated to be 8.9% [95% confidence interval (CI) 5.3-14.5], while in DLB was estimated to be 30.8% (±23.4 to 39.3). Verbal hallucinations, perceived as originating outside the head, were the most common form of AH. Non-verbal AH were also common while musical AH were rare. VH were more prevalent, with an estimated pooled prevalence in PD of 28.2% (±19.1 to 39.5), while in DLB they were estimated to be 61.8% (±49.1 to 73.0). Meta-regression determined that the use of validated methodologies to identify hallucinations produced higher prevalence estimates. CONCLUSIONS: AH and VH present in a substantial proportion of PD and DLB cases, with VH reported more frequently in both conditions. Both AH and VH are more prevalent in DLB than PD. There is a need for standardised use of validated methods to detect and monitor hallucinations.

Commissural Gain Control Enhances the Midbrain Representation of Sound Location.

Accurate localization of sound sources is essential for survival behavior in many species. The inferior colliculi (ICs) are the first point in the auditory pathway where cues used to locate sounds, ie, interaural time differences (ITDs), interaural level differences (ILDs), and pinna spectral cues, are all represented in the same location. These cues are first extracted separately on each side of the midline in brainstem nuclei that project to the ICs. Because of this segregation, each IC predominantly represents stimuli in the contralateral hemifield. We tested the hypothesis that commissural connections between the ICs mediate gain control that enhances sound localization acuity. We recorded IC neurons sensitive to either ITDs or ILDs in anesthetized guinea pig, before, during, and following recovery from deactivation of the contralateral IC by cryoloop cooling or microdialysis of procaine. During deactivation, responses were rescaled by divisive gain change and additive shifts, which reduced the dynamic range of ITD and ILD response functions and the ability of neurons to signal changes in sound location. These data suggest that each IC exerts multiplicative gain control and subtractive shifts over the other IC that enhances the neural representation of sound location. Furthermore, this gain control operates in a similar manner on both ITD- and ILD-sensitive neurons, suggesting a shared mechanism operates across localization cues. Our findings reveal a novel dependence of sound localization on commissural processing. SIGNIFICANCE STATEMENT: Sound localization, a fundamental process in hearing, is dependent on bilateral computations in the brainstem. How this information is transmitted from the brainstem to the auditory cortex, through several stages of processing, without loss of signal fidelity, is not clear. We show that the ability of neurons in the auditory midbrain to encode azimuthal sound location is dependent on gain control mediated by the commissure of the inferior colliculi. This finding demonstrates that commissural processing between homologous auditory nuclei, on either side of the midline, enhances the precision of sound localization.

Intercollicular commissural connections refine the representation of sound frequency and level in the auditory midbrain.

Connections unifying hemispheric sensory representations of vision and touch occur in cortex, but for hearing, commissural connections earlier in the pathway may be important. The brainstem auditory pathways course bilaterally to the inferior colliculi (ICs). Each IC represents one side of auditory space but they are interconnected by a commissure. By deactivating one IC in guinea pig with cooling or microdialysis of procaine, and recording neural activity to sound in the other, we found that commissural input influences fundamental aspects of auditory processing. The areas of nonV frequency response areas (FRAs) were modulated, but the areas of almost all V-shaped FRAs were not. The supra-threshold sensitivity of rate level functions decreased during deactivation and the ability to signal changes in sound level was decremented. This commissural enhancement suggests the ICs should be viewed as a single entity in which the representation of sound in each is governed by the other.

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity.

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other.