Katherine C. Wood

Preference for natural: instrumental and ideational/moral motivations, and the contrast between foods and medicines

Preference for natural refers to the fact that in a number of domains, especially food, people prefer natural entities to those which have been produced with human intervention. Two studies with undergraduate students and representative American adults indicate that the preference for natural is substantial, and stronger for foods than for medicines. Although healthfulness is often given as a reason for preferring natural foods, even when healthfulness or effectiveness (for medicines) of the natural and artificial exemplars is specified as equivalent, the great majority of people who demonstrate a preference for natural continue to prefer natural. In addition, when the natural and artificial exemplars are specified to be chemically identical, a majority of people who prefer natural continue to prefer it. This suggests that a substantial part of the motivation for preferring natural is ideational (moral or aesthetic), as opposed to instrumental (healthiness/effectiveness or superior sensory properties).

Picomolar nitric oxide signals from central neurons recorded using ultrasensitive detector cells.

Background: The biological actions of NO depend critically on its concentration, which is very difficult to measure. Results: Recorded using the most sensitive detectors yet described, NO levels synthesized by activated brain neurons generally were in the picomolar range but varied regionally. Conclusion: NO operates physiologically at the subnanomolar concentrations that selectively target its guanylyl cyclase-linked receptors. Significance: Physiological NO levels are far lower than commonly supposed. Nitric oxide (NO) is a widespread signaling molecule with potentially multifarious actions of relevance to health and disease. A fundamental determinant of how it acts is its concentration, but there remains a lack of coherent information on the patterns of NO release from its sources, such as neurons or endothelial cells, in either normal or pathological conditions. We have used detector cells having the highest recorded NO sensitivity to monitor NO release from brain tissue quantitatively and in real time. Stimulation of NMDA receptors, which are coupled to activation of neuronal NO synthase, routinely generated NO signals from neurons in cerebellar slices. The average computed peak NO concentrations varied across the anatomical layers of the cerebellum, from 12 to 130 pm. The mean value found in the hippocampus was 200 pm. Much variation in the amplitudes recorded by individual detector cells was observed, this being attributable to their location at variable distances from the NO sources. From fits to the data, the NO concentrations at the source surfaces were 120 pm to 1.4 nm, and the underlying rates of NO generation were 36–350 nm/s, depending on area. Our measurements are 4–5 orders of magnitude lower than reported by some electrode recordings in cerebellum or hippocampus. In return, they establish coherence between the NO concentrations able to elicit physiological responses in target cells through guanylyl cyclase-linked NO receptors, the concentrations that neuronal NO synthase is predicted to generate locally, and the concentrations that neurons actually produce.

Improved genetically-encoded, FlincG-type fluorescent biosensors for neural cGMP imaging.

Genetically-encoded biosensors are powerful tools for understanding cellular signal transduction mechanisms. In aiming to investigate cGMP signaling in neurones using the EGFP-based fluorescent biosensor, FlincG (fluorescent indicator for cGMP), we encountered weak or non-existent fluorescence after attempted transfection with plasmid DNA, even in HEK293T cells. Adenoviral infection of HEK293T cells with FlincG, however, had previously proved successful. Both constructs were found to harbor a mutation in the EGFP domain and had a tail of 17 amino acids at the C-terminus that differed from the published sequence. These discrepancies were systematically examined, together with mutations found beneficial for the related GCaMP family of Ca2+ biosensors, in a HEK293T cell line stably expressing both nitric oxide (NO)-activated guanylyl cyclase and phosphodiesterase-5. Restoring the mutated amino acid improved basal fluorescence whereas additional restoration of the correct C-terminal tail resulted in poor cGMP sensing as assessed by superfusion of either 8-bromo-cGMP or NO. Ultimately, two improved FlincGs were identified: one (FlincG2) had the divergent tail and gave moderate basal fluorescence and cGMP response amplitude and the other (FlincG3) had the correct tail, a GCaMP-like mutation in the EGFP region and an N-terminal tag, and was superior in both respects. All variants tested were strongly influenced by pH over the physiological range, in common with other EGFP-based biosensors. Purified FlincG3 protein exhibited a lower cGMP affinity (0.89 μM) than reported for the original FlincG (0.17 μM) but retained rapid kinetics and a 230-fold selectivity over cAMP. Successful expression of FlincG2 or FlincG3 in differentiated N1E-115 neuroblastoma cells and in primary cultures of hippocampal and dorsal root ganglion cells commends them for real-time imaging of cGMP dynamics in neural (and other) cells, and in their subcellular specializations.

Cortical inhibitory interneurons control sensory processing

Inhibitory and excitatory neurons form intricate interconnected circuits in the mammalian sensory cortex. Whereas the function of excitatory neurons is largely to integrate and transmit information within and between brain areas, inhibitory neurons are thought to shape the way excitatory neurons integrate information, and they exhibit context-specific and behavior-specific responses. Over the last few years, work across sensory modalities has begun unraveling the function of distinct types of cortical inhibitory neurons in sensory processing, identifying their contribution to controlling stimulus selectivity of excitatory neurons and modulating information processing based on the behavioral state of the subject. Here, we review results from recent studies and discuss the implications for the contribution of inhibition to cortical circuit activity and information processing.

Integration of Visual Information in Auditory Cortex Promotes Auditory Scene Analysis through Multisensory Binding

Summary How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

Multiplexed and multivariate representations of sound identity during perceptual constancy

Perceptual constancy describes the ability to represent objects in the world across variation in sensory input such as recognizing a person from different angles or a spoken word across talkers. This ability requires neural representations that are sensitive to some aspects of a stimulus (such as the spectral envelope of a sound) while tolerant to other variations in stimuli (such periodicity). In hearing, such representations have been observed in auditory cortex but never in combination with behavioural testing, which is essential in order to link neural codes to perceptual constancy. By testing ferrets in a vowel discrimination task which they perform across multiple stimulus dimensions and recording neuronal activity in auditory cortex we directly correlate neural tolerance with perceptual constancy. Subjects reported vowel identity across variations in fundamental frequency, sound location, and sound level, but failed to consistently generalize across voicing from voiced to whispered sounds. We decoded the responses of simultaneously recorded units in auditory cortex to identity units informative about vowel identity across each of these task-orthogonal variations in acoustic input. Significant proportions of units were vowel informative across each of these conditions, although fewer units were informative about vowel identity across voicing. For about half of vowel informative units, information about vowel identity was conserved across multiple orthogonal variables. The time of best decoding was also used to identify the relative timing and temporal multiplexing of sound features. Our results show that neural tolerance can be observed within single units in auditory cortex in animals demonstrating perceptual constancy.

Simultaneous Assessment of Speech Identification and Spatial Discrimination A Potential Testing Approach for Bilateral Cochlear Implant Users

With increasing numbers of children and adults receiving bilateral cochlear implants, there is an urgent need for assessment tools that enable testing of binaural hearing abilities. Current test batteries are either limited in scope or are of an impractical duration for routine testing. Here, we report a behavioral test that enables combined testing of speech identification and spatial discrimination in noise. In this task, multitalker babble was presented from all speakers, and pairs of speech tokens were sequentially presented from two adjacent speakers. Listeners were required to identify both words from a closed set of four possibilities and to determine whether the second token was presented to the left or right of the first. In Experiment 1, normal-hearing adult listeners were tested at 15° intervals throughout the frontal hemifield. Listeners showed highest spatial discrimination performance in and around the frontal midline, with a decline at more eccentric locations. In contrast, speech identification abilities were least accurate near the midline and showed an improvement in performance at more lateral locations. In Experiment 2, normal-hearing listeners were assessed using a restricted range of speaker locations designed to match those found in clinical testing environments. Here, speakers were separated by 15° around the midline and 30° at more lateral locations. This resulted in a similar pattern of behavioral results as in Experiment 1. We conclude, this test offers the potential to assess both spatial discrimination and the ability to use spatial information for unmasking in clinical populations.

Primary auditory cortex represents the location of sound sources in a cue-invariant manner

Auditory cortex is required for sound localisation, but how neural firing in auditory cortex underlies our perception of sources in space remains unknown. We measured spatial receptive fields in animals actively attending to spatial location while they performed a relative localisation task using stimuli that varied in the spatial cues that they provided. Manipulating the availability of binaural and spectral localisation cues had mild effects on the ferret’s performance and little impact on the spatial tuning of neurons in primary auditory cortex (A1). Consistent with a representation of space, a subpopulation of neurons encoded spatial position across localisation cue types. Spatial receptive fields measured in the presence of a competing sound source were sharper than those measured in a single-source configuration. Together these observations suggest that A1 encodes the location of auditory objects as opposed to spatial cue values. We compared our data to predictions generated from two theories about how space is represented in auditory cortex: The two-channel model, where location is encoded by the relative activity in each hemisphere, and the labelled-line model where location is represented by the activity pattern of individual cells. The representation of sound location in A1 was mainly contralateral but peak firing rates were distributed across the hemifield consistent with a labelled line model in each hemisphere representing contralateral space. Comparing reconstructions of sound location from neural activity, we found that a labelled line architecture far outperformed two channel systems. Reconstruction ability increased with increasing channel number, saturating at around 20 channels. Significance statement Our perception of a sound scene is one of distinct sound sources each of which can be localised, yet auditory space must be computed from sound location cues that arise principally by comparing the sound at the two ears. Here we ask: (1) do individual neurons in auditory cortex represent space, or sound localisation cues? (2) How is neural activity ‘read out’ for spatial perception? We recorded from auditory cortex in ferrets performing a localisation task and describe a subpopulation of neurons that represent space across localisation cues. Our data are consistent with auditory space being read out using the pattern of activity across neurons (a labelled line) rather than by averaging activity within each hemisphere (a two-channel model).

Multisensory stimuli improve relative localisation judgments compared to unisensory auditory or visual stimuli

Observers performed a relative localisation task in which they reported whether the second of two sequentially presented signals occurred to the left or right of the first. Stimuli were detectability-matched auditory, visual, or auditory-visual signals and the goal was to compare changes in performance with eccentricity across modalities. Visual performance was superior to auditory at the midline, but inferior in the periphery, while auditory-visual performance exceeded both at all locations. No such advantage was seen when performance for auditory-only trials was contrasted with trials in which the first stimulus was auditory-visual and the second auditory only.