Sensory Response Properties Research Articles

Nutritional and technological aspects of barley β-glucan enriched biscuits containing isomaltulose as sucrose replacer

The objective of this work was to evaluate the physicochemical, sensory and potential glycemic response properties of a biscuit (β-GB) containing barley β-glucan at 6% w/w, sufficient to satisfy the EFSA's health claims related to cholesterol lowering and fecal bulk increase, and isomaltulose as sweetener. The freshly prepared β-GB was softer (p < 0.05) than the control biscuit (formulated with sucrose and without β-glucan); differences in hardness between the two biscuit formulations diminished during storage. The glucose release kinetics, evaluated by an in vitro enzymic assay, showed that after 5 h of digestion, glucose release was significantly (p < 0.05) lower for the β-GB (16.4%) compared to the control (26.4%) or to several commercial products of similar composition, which were lacking the β-glucan as ingredient (22.7 – 33.7%). The extent of in vitro glucose released was negatively correlated (r = -0.72; p = 0.020) to the viscosity values of ‘physiological extracts’ enclosed in dialysis tubes after 5 h incubation, and to their total dietary fiber content (r = -0.79; p = 0.006) after 20 min of digestion. The fortified biscuits with β-glucan and isomaltulose were found to be satisfactory in terms of flavor, sweetness, and texture by a group of “diabetic individuals” who rated these products highly, with an average of 5.8, in a 7-point hedonic overall acceptability scale. The low extent of glucose released along with the sensory results suggested that isomaltulose containing biscuits fortified with β-glucans could simultaneously provide various health benefits and be highly acceptable by consumers with glucose metabolism disorders.

Early life neuroimmune interactions modulate neonatal nociceptive priming

Young children perceive nociceptive stimuli and experience pain differently than adults, but the underlying mechanisms that cause these differential effects are unknown. The result of this uncertainty can lead to incomplete pain management for these patients. Further, a vulnerable period occurs during early life whereby aversive stimuli can be biologically encoded possibly through altered neuroimmune and endocrine interactions that influence sensory responsiveness later in life. We evaluated the role of neuroimmune and endocrine interactions in early life, and explored the effects on “neonatal priming.” We assessed pain-like behaviors, sensory neuron response properties with ex vivo electrophysiology, and dorsal root ganglion (DRG) and macrophage specific gene expression under normal and/or genetically altered conditions in both uninjured mice and in animals that experienced surgical hindpaw incisions. We first found that sensory neuron deletion of the receptor for the endocrine signaling molecule growth hormone (GH), induced pain-like behaviors in neonates. Acute peripheral sensitization after incision injury was prevented by local GH treatment, and macrophage ablation of GH receptor also prevented incision-related effects. Macrophages appear to sequester injury-site GH, which releases a tonic inhibition on the sensory neurons and drives primary afferent sensitization. Manipulations in GH signaling or ablating neonatal macrophages was found to be critical for the development of neonatal priming. New ATAC-seq data indicates differences in chromatin accessibility in immature macrophages that may underlie how early life neuroimmune interactions modulate neonatal priming effects. Results demonstrate that the periphery has unique modulators of neonatal nociception that often require distinct immune cell and endocrine signaling activities that influence sensory neuron function. We are currently investigating how altering this process may affect neonatal priming through epigenetic modifications in macrophages. R01NS105715.

Parallel Lemniscal and Non-Lemniscal Sources Control Auditory Responses in the Orbitofrontal Cortex (OFC).

The orbitofrontal cortex (OFC) controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure oddball detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed oddball detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals, if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus, the baseline sensory responses allow the behavioral requirement-based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurologic disorders can lead to behavioral deficits.

Multiparametric assessment of the impact of opsin expression and anesthesia on striatal cholinergic neurons and auditory brainstem activity.

Recent developments in genetic engineering have established murine models that permit the selective control of cholinergic neurons via optical stimulation. Despite copious benefits granted by these experimental advances, the sensory physiognomy of these organisms has remained poorly understood. Therefore, the present study evaluates sensory and neuronal response properties of animal models developed for the study of optically induced acetylcholine release regulation. Auditory brainstem responses, fluorescence imaging, and patch clamp recording techniques were used to assess the impact of viral infection, sex, age, and anesthetic agents across the ascending auditory pathway of ChAT-Cre and ChAT-ChR2(Ai32) mice. Data analyses revealed that neither genetic configuration nor adeno-associated viral infection alters the early stages of auditory processing or the cellular response properties of cholinergic neurons. However, anesthetic agent and dosage amount profoundly modulate the response properties of brainstem neurons. Last, analyses of age-related hearing loss in virally infected ChAT-Cre mice did not differ from those reported in wild type animals. This investigation demonstrates that ChAT-Cre and ChAT-ChR2(Ai32) mice are viable models for the study of cholinergic modulation in auditory processing, and it emphasizes the need for prudence in the selection of anesthetic procedures.

Correlating Anatomy and Function with Gene Expression in Individual Neurons by Combining in Vivo Labeling, Patch Clamp, and Single Cell RNA-seq.

The classification of neurons into distinct types is an ongoing effort aimed at revealing and understanding the diversity of the components of the nervous system. Recently available methods allow us to determine the gene expression pattern of individual neurons in the mammalian cerebral cortex to generate powerful categorization schemes. For a thorough understanding of neuronal diversity such genetic categorization schemes need to be combined with traditional classification parameters like position, axonal projection or response properties to sensory stimulation. Here we describe a method to link the gene expression of individual neurons with their position, axonal projection, or sensory response properties. Neurons are labeled in vivo based on their anatomical or functional properties and, using patch clamp pipettes, their RNA individually harvested in vitro for RNAseq. We validate the methodology using multiple established molecularly and anatomically distinct cell populations and explore molecular differences between uncharacterized neurons in mouse visual cortex. Gene expression patterns between L5 neurons projecting to frontal or contralateral cortex are distinct while L2 neurons differing in position, projection, or function are molecularly similar. With this method we can determine the genetic expression pattern of functionally and anatomically identified individual neurons.

1/f Characteristic in Natural Signals and Sensory Neural Response Properties

1/f Characteristic in Natural Signals and Sensory Neural Response Properties

Functional response properties of VIP-expressing inhibitory neurons in mouse visual and auditory cortex.

Despite accounting for about 20% of all the layer 2/3 inhibitory interneurons, the vasoactive intestinal polypeptide (VIP) expressing neurons remain the least thoroughly studied of the major inhibitory subtypes. In recent studies, VIP neurons have been shown to be activated by a variety of cortico-cortical and neuromodulatory inputs, but their basic sensory response properties remain poorly characterized. We set out to explore the functional properties of layer 2/3 VIP neurons in the primary visual (V1) and primary auditory cortex (A1), using two-photon imaging guided patch recordings. We found that in the V1, VIP neurons were generally broadly tuned, with their sensory response properties resembling those of parvalbumin (PV) expressing neurons. With the exception of response latency, they did not exhibit a significant difference from PV neurons across any of the properties tested, including overlap index, response modulation, orientation selectivity, and direction selectivity. In the A1, on the other hand, VIP neurons had a strong tendency to be intensity selective, which is a property associated with a subset of putative pyramidal cells and virtually absent in PV neurons. VIP neurons had a best intensity that was significantly lower than that of PV and putative pyramidal neurons. Finally, sensory evoked spike responses of VIP neurons were delayed relative to pyramidal and PV neurons in both the V1 and A1. Combined, these results demonstrate that the sensory response properties of VIP neurons do not fit a simple model of being either PV-like broadly tuned or pyramidal-like narrowly tuned. Instead, the selectivity pattern varies with sensory area and can even be, as in the case of low sound intensity responsiveness, distinct from both PV and pyramidal neurons.

In vivo odourant response properties of migrating adult-born neurons in the mouse olfactory bulb.

Juxtaglomerular neurons (JGNs) of the mammalian olfactory bulb are generated throughout life. Their integration into the preexisting neural network, their differentiation and survival therein depend on sensory activity, but when and how these adult-born cells acquire responsiveness to sensory stimuli remains unknown. In vivo two-photon imaging of retrovirally labelled adult-born JGNs reveals that ~90% of the cells arrive at the glomerular layer after day post injection (DPI) 7. After arrival, adult-born JGNs are still migrating, but at DPI 9, 52% of them have odour-evoked Ca(2+) signals. Their odourant sensitivity closely resembles that of the parent glomerulus and surrounding JGNs, and their spontaneous and odour-evoked spiking is similar to that of their resident neighbours. Our data reveal a remarkably rapid functional integration of adult-born cells into the preexisting neural network. The mature pattern of odour-evoked responses of these cells strongly contrasts with their molecular phenotype, which is typical of immature, migrating neuroblasts.

The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing

SummarySensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.

Hearing in action; auditory properties of neurons in the red nucleus of alert primates.

The response of neurons in the Red Nucleus pars magnocellularis (RNm) to both tone bursts and electrical stimulation were observed in three cynomolgus monkeys (Macaca fascicularis), in a series of studies primarily designed to characterize the influence of the dopaminergic ventral midbrain on auditory processing. Compared to its role in motor behavior, little is known about the sensory response properties of neurons in the red nucleus (RN); particularly those concerning the auditory modality. Sites in the RN were recognized by observing electrically evoked body movements characteristic for this deep brain structure. In this study we applied brief monopolar electrical stimulation to 118 deep brain sites at a maximum intensity of 200 μA, thus evoking minimal body movements. Auditory sensitivity of RN neurons was analyzed more thoroughly at 15 sites, with the majority exhibiting broad tuning curves and phase locking up to 1.03 kHz. Since the RN appears to receive inputs from a very early stage of the ascending auditory system, our results suggest that sounds can modify the motor control exerted by this brain nucleus. At selected locations, we also tested for the presence of functional connections between the RN and the auditory cortex by inserting additional microelectrodes into the auditory cortex and investigating how action potentials and local field potentials (LFPs) were affected by electrical stimulation of the RN.

GABAergic synapses: their plasticity and role in sensory cortex.

The mammalian neocortex is composed of a variety of cell types organized in a highly interconnected circuit. GABAergic neurons account for only about 20% of cortical neurons. However, they show widespread connectivity and a high degree of diversity in morphology, location, electrophysiological properties and gene expression. In addition, distinct populations of inhibitory neurons have different sensory response properties, capacities for plasticity and sensitivities to changes in sensory experience. In this review we summarize experimental evidence regarding the properties of GABAergic neurons in primary sensory cortex. We will discuss how distinct GABAergic neurons and different forms of GABAergic inhibitory plasticity may contribute to shaping sensory cortical circuit activity and function.

The emergence of functional microcircuits in visual cortex

Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured1–4 and excitatory neurons form subnetworks that process related sensory information5,6. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly related patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were highly selective for visual stimuli already at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganised extensively, as more connections formed selectively between neurons with similar visual responses, and connections were eliminated between visually unresponsive neurons, while the overall connectivity rate did not change. We propose a unified model of cortical microcircuit development based on activity-dependent mechanisms of plasticity: neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience – a process that may be facilitated by early electrical coupling between neuronal subsets7–9 – after which patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.

Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing

Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response.

The Impact of an LGNd Impulse on the Awake Visual Cortex: Synaptic Dynamics and the Sustained/Transient Distinction

We used spike-triggered current source-density analysis to examine axonal and postsynaptic currents generated in the visual cortex of awake rabbits by spontaneous spikes of individual sustained and transient dorsal lateral geniculate nucleus (LGNd) neurons. Using these data, we asked whether sustained/transient sensory responses are related to short-term synaptic dynamics at the thalamocortical synapse. Most sustained (34 of 40) and transient (24 of 25) neurons generated axonal and monosynaptic responses in layer 4 and/or 6 of the aligned cortical domain, with input from transient neurons arriving approximately 0.3 ms earlier and 100-200 microm deeper. Postsynaptic cortical responses generated by both thalamic cell classes were reduced in amplitude after a preceding impulse and slowly recovered over a period of >750 ms. We interpret this to reflect interval-dependent recovery from chronic depression at the thalamocortical synapse, caused by significant spontaneous firing of LGNd cells (approximately 8 Hz). Surprisingly, postsynaptic cortical responses generated by spontaneous spikes of sustained thalamic neurons were more depressed than those of transient neurons. This difference was seen both in layers 4 and 6. The depression saturated rapidly with multiple preceding impulses, and postsynaptic responses generated by sustained neurons during maintained visual stimulation remained sufficiently robust to allow a sustained flow of information to the cortex. Our results indicate a relationship between the sensory response properties of thalamic neurons and the short-term dynamics of their synapses, and suggest that cortical recipients of sustained and transient thalamic inputs will differ considerably in their response modulation by prior impulse activity.

A parietal–temporal sensory–motor integration area for the human vocal tract: Evidence from an fMRI study of skilled musicians

Several sensory–motor integration regions have been identified in parietal cortex, which appear to be organized around motor-effectors (e.g., eyes, hands). We investigated whether a sensory–motor integration area might exist for the human vocal tract. Speech requires extensive sensory–motor integration, as does other abilities such as vocal musical skills. Recent work found that a posterior superior temporal-parietal region, area Spt, has both sensory (auditory) and motor response properties (for both speech and tonal stimuli). Brain activity of skilled pianists was measured with fMRI while they listened to a novel melody and either covertly hummed the melody (vocal tract effectors) or covertly played the melody on a piano (manual effectors). Activity in area Spt was significantly higher for the covert hum versus covert play condition. A region in the anterior IPS (aIPS) showed the reverse pattern, suggesting its involvement in sensory-manual transformations. This finding suggests that area Spt is a sensory–motor integration area for vocal tract gestures.

Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling.

How individual receptive field properties are formed in the maturing sensory neocortex remains largely unknown. The shortening of N-methyl-d-aspartate (NMDA) receptor currents by 2A subunit (NR2A) insertion has been proposed to delimit the critical period for experience-dependent refinement of circuits in visual cortex. In mice engineered to maintain prolonged NMDA responses by targeted deletion of NR2A, the sensitivity to monocular deprivation was surprisingly weakened but restricted to the typical critical period and delayed normally by dark rearing from birth. Orientation preference instead failed to mature, occluding further effects of dark rearing. Interestingly, a full ocular dominance plasticity (but not orientation bias) was selectively restored by enhanced inhibition, reflecting an imbalanced excitation in the absence of NR2A. Many of the downstream pathways involved in NMDA signaling are coupled to the receptor through a variety of protein-protein interactions and adaptor molecules. To further investigate a mechanistic dissociation of receptive field properties in the developing visual system, mice carrying a targeted disruption of the NR2A-associated 95-kDa postsynaptic density (PSD95) scaffolding protein were analyzed. Although the development and plasticity of ocular dominance was unaffected, orientation preference again failed to mature in these mice. Taken together, our results demonstrate that the cellular basis generating individual sensory response properties is separable in the developing neocortex.

Somatosensory cortical neuronal population activity across states of anaesthesia.

Experiments were carried out to learn about changes in sensory cortical processing associated with different levels of anaesthesia. Traditionally this question has been addressed by studying single neurons. Because state changes are likely to influence the relationships between neurons, the present experiments were undertaken to investigate the spatial and temporal firing patterns distributed across cortex. Using 5 x 5 or 10 x 10 microelectrode arrays, spontaneous and stimulus-evoked activity of multineuron clusters was recorded from rat somatosensory 'barrel' cortex (the whisker representation) during a light surgical stage of urethane anaesthesia, and after two supplemental doses of urethane which led to intermediate and deep levels of anaesthesia. At all depths of anaesthesia, spontaneously occurring action potentials at a single electrode tended to be clustered into 'bursts.' With increasing anaesthetic depth, bursts became more prominent and rhythmic, and increasingly synchronized between cortical barrel-columns. Burst frequency decreased and fewer spikes occurred outside bursts, leading to a decrease in the overall spontaneous firing rate. The cortical territory engaged by individual whiskers contracted with increasing depth of anaesthesia, leading to the spatial segregation of whisker representations. At all stages of anaesthesia, whisker stimulation produced the maximal cortical response when delivered close to burst onset. These observations show that ongoing spontaneous activity modulates sensory response properties and makes peripheral tactile information accessible to a cortical territory whose size is determined by the phase of burst cycle. The possible significance of the cyclic cortical responsiveness encountered during urethane anaesthesia to cortical processing in awake rats is considered.

Sensory response properties of cortical neurons in the anterior ectosylvian sulcus of cats: intracellular recording and labeling

Visual and auditory sensory responses of cortical neurons in the caudal half of the anterior ectosylvian sulcus (AES) of cats were examined under α-chloralose anesthesia, using intracellular recording and labeling techniques. Stable intracellular recordings were obtained from 155 neurons, and 141 neurons exhibited responses to sensory stimuli. Of 141 sensory neurons, 74 (52%) were bimodal neurons that responded to both visual and auditory stimuli, and 67 (48%) were unimodal showing sensory responses only to visual (25) or auditory stimulation (42). Forty-five neurons (35 pyramidal neurons, 5 non-pyramidal neurons, 5 not classified) responsive to sensory stimuli were labeled with biocytin. The percentage of bimodal neurons of the biocytin-labeled neurons was 40% ( 4 10 ) in layer II, 50% ( 10 20 ) in layer III–IV, 70% ( 7 10 ) in layer V and 60%/) ( 3 5 ) in layer VI. Thus the convergence of visual and auditory inputs on single neurons was most intense in layer V. Auditory response latencies were in a narrow range from 10 to 40 ms, whereas visual response latencies were in a wide range from 15 to 100 ms. Late visual responses (> 60 ms) were more commonly elicited in bimodal neurons than in visual unimodal neurons. Visual responses in layer 11 were all elicited over 40 ms, whereas early visual responses within 40 ms were observed in the other cortical layers. A subgroup of neurons ( 22 141 ) had a propensity to exhibit a burst discharge, a train of three to seven action potentials on a deploarizing envelope in response to sensory stimuli. Their specific distribution in cortical tissue was suggested by the result that six out of nine biocytin-labeled neurons (seven pyramidal neurons, two non-pyramidal neurons) showing burst discharges to sensory stimuli were observed in layer V. These results are considered to signify some aspects of intracortical organization related to the cross-modal integration of sensory inputs.

Behavioral modulation of sensory responses of primate putamen neurons

Sensory response properties of putamen neurons were investigated in 4 awake macaque monkeys while the animals performed GO/NO-GO tasks guided by sensory stimuli. In the GO condition, visual stimuli served as a trigger for a sequence of repetitive elbow flexion-extensions and auditory stimuli served as a trigger for orofacial movements, while the identical sensory stimuli required the animals to withhold movements in the NO-GO condition. Short latency responses to visual and/or auditory stimuli were observed in 206 type I cells with tonic discharges at about 2–7 Hz, with a characteristic discharge rhythm and in 57 type II cells with low spontaneous discharge rates, usually less than 0.5 Hz, which showed burst discharges during the tasks. Most of these cells (163/206 type I cells, 52/57 type II cells) responded differentially to identical sensory stimuli presented in the GO and NO-GO conditions. The responses to sensory stimuli presented in the GO condition were much larger in 67% of type I cells and 58% of type II cells than the responses to identical stimuli presented in the NO-GO condition. On the other hand, 12% of type I and 33% of type II cells showed larger responses in the NO-GO than in the GO condition. It is suggested that the strong behavioral modulation of striatal sensory responses serves as a mechanism to start the neural processes for preparation and/or initiation or withholding of particular movements associated with learned sensory stimuli.

Sensory response of cortical neurons in the anterior ectosylvian sulcus, including the area evoking eye movement

The deep cortical tissue in the caudal portion of the anterior ectosylvian sulcus (AES) of cats anesthetized with alpha-chloralose was explored to examine the sensory response properties of neurons in this area, which is known to contain an area evoking eye movement. Of 873 neurons isolated, 262 (30.0%) were multimodal, i.e. responsive to two or more of the stimulus modalities of visual, auditory, or somatic. The ratio of multimodal neurons to total neurons in the eye-movement-evoking area was significantly larger than this ratio in other areas; 79 (39.5%) of 200 neurons in the eye-movement-evoking area were multimodal, while 183 (27.2%) of 673 neurons in other areas were multimodal. Neuronal minimal latency in response to visual stimulation was widely and bimodally distributed, showing two peaks at 35 ms and 60 ms, whereas latencies to auditory and somatic stimulation were narrowly distributed, with one peak at 10 ms and 15 ms, respectively. There was no remarkable difference either between unimodal neurons and multimodal neurons or between the neurons in the eye-movement-evoking area and those in other areas in distribution of latency. That there was a significant difference in ratio of multimodal to total neurons between the eye movement area and other areas suggests that some convergence or integration of different kinds of sensory input in relation to eye movement might be carried out in the caudal portion of the AES.