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Biology subjects

Town, S. M.

Publications and source records attributed to Town, S. M..

9 recordsLinked to original sources

Cortical cooling reveals a role for visual cortex in generating visual responses in auditory cortex

Multisensory integration is a fundamental feature of cortical processing, yet the functional pathways that deliver visual signals to the auditory cortex remain poorly understood. While anatomical studies reveal multiple candidate projection routes, demonstrating their causal contribution requires targeted manipulation of neural activity. Here, we used cortical cooling to reversibly inactivate the posteromedial lateral suprasylvian cortex (PMLS) and the adjacent area 21 to determine the functional role of higher-order visual areas in generating visual responses within the auditory cortex of the ferret. Units responsive to sound, light, or combined audiovisual stimuli were found across all sampled auditory fields and cortical depths, with visual responses most prominent within the infragranular layers and the non-tonotopic secondary auditory cortex of the Anterior Ectosylvian Gyrus (AEG). Cortical cooling induced robust, bi-directional, and stimulus-specific modulations of firing rates in AC. Approximately 50% of visually responsive units exhibited a significant decrease or complete elimination of visual activity during cooling, confirming a functional role for visual input from PLMS/area 21 to AC. Surprisingly, cooling also revealed circuit-level complexities: a subset ([~]5%) of units showed enhanced or newly emergent visual responses during inactivation, suggesting that PMLS/area 21 normally exerts a gating influence over alternative visual pathways. Furthermore, contrary to feedforward anatomical predictions, neurons in the AEG--the region most heavily innervated by the cooled visual areas --were less frequently impacted by cooling than those in PEG. Together, these findings demonstrate that higher visual areas causally shape cross-modal processing in the auditory cortex through a complex mixture of direct excitation and network-level modulation.

neuroscience↗

Head-Centred Sound Localisation Behaviour Reveals Head and World Centered Reference Frames in Auditory Cortex

The auditory system relies on head-centered localisation cues to estimate sound source position. Yet listeners and single neurons can encode sound in world-centred spatial reference frames. However, most studies of sound localisation constrain the subjects orientation within a fixed speaker ring, making it difficult to distinguish which reference frame underlies spatial coding. We utilised a sound localisation task that required ferrets localise sound location, relative to the head, across rotations in the starting platform within the testing arena. Two ferrets were trained to discriminate front from back sounds. Once trained, the orientation of both the central platform and the target speakers were rotated between testing sessions, retaining the task contingency in head-centered coordinates, but breaking the alignment of head and world centered reference frames. Probe trials were presented from the other speakers so that spatial receptive fields could be constructed and compared across central platform rotations. Neural activity was recorded from auditory cortex using chronically implanted 32-channel arrays. Across 1,777 recorded units, 596 were stimulus driven. Spatially tuned neurons were predominantly head-centred, with 208 and 232 units classified as head-centred in the two animals, compared with 48 and 49 world-centred units and 33 and 26 un-tuned units, respectively. Temporal analysis showed that most units retained the same reference-frame classification from onset to offset, but the magnitude of their head-versus-world preference diminished over time, with offset responses shifting towards more ambiguous and, in some cases, world-centred coding. Together, these results demonstrate that auditory cortex maintains parallel head centered and allocentric representations that are head dominated at onset but incorporate increased world-centred information at offset, supporting perceptual constancy during dynamic listening.

neuroscience↗

Reversible inactivation of ferret auditory cortex impairs spatial and non-spatial hearing

A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features such as sound location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and non-spatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n=2) or optogenetics (n=1). In optogenetic experiments, we utilized the mDLx promoter to express Channelrhodopsin 2 in GABAergic interneurons and confirmed both viral expression (n=2) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia (n=465 units from 2 additional untrained ferrets). Cortical inactivation impaired vowel discrimination in co-located noise, but not in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180{degrees}. Testing the ferrets implanted with cooling loops in a sound localization task confirmed that deficits in spatial hearing arose from inactivation of the same region of auditory cortex that was implicated in vowel discrimination in noise. Our results are consistent with single unit recordings in primary auditory cortex showing mixed selectivity for spatial and non-spatial features of sound and suggest a contribution of this region to multiple forms of hearing necessary for auditory scene analysis. Significance StatementNeurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and non- spatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin 2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia.

neuroscience↗

Sound localization in world and head-centeredspace in ferrets

The location of sounds can be described in multiple coordinate systems that are defined relative to ourselves, or the world around us. Evidence from neural recordings in animals point towards the existence of both head-centered and world-centered representations of sound location in the brain; however, it is unclear whether such neural representations have perceptual correlates in the sound localization abilities of non-human listeners. Here, we establish novel behavioral tests to determine the coordinate systems in which ferrets can localize sounds. We found that ferrets could learn to discriminate between sound locations that were fixed in either world-centered or head-centered space, across wide variations in sound location in the alternative coordinate system. Using probe sounds to assess broader generalization of spatial hearing, we demonstrated that in both head and world-centered tasks, animals used continuous maps of auditory space to guide behavior. Single trial responses of individual animals were sufficiently informative that we could then model sound localization using speaker position in specific coordinate systems and accurately predict ferrets actions in held-out data. Our results indicate that an animal model in which neurons are known to be tuned to sound location in egocentric and allocentric reference frames can also localize sounds in multiple head and world-centered spaces. Significance StatementHumans can describe the location of sounds either relative to themselves, or in the world, independent of their momentary position. These different spaces are also represented in the activity of neurons in animals, but its not clear whether non-human listeners also perceive both head and world-centered sound location. Here, we designed two behavioral tasks in which ferrets had to discriminate between two sounds using their position in the world, or relative to the head. Subjects learnt to solve both problems and showed the ability to generalize sound location in each space when presented with infrequent probe sounds. These findings reveal a perceptual correlate of neural sensitivity previously observed in the ferret brain and establish that, like humans, ferrets can access an auditory map of their local environment.

animal behavior and cognition↗

Hippocampal theta oscillations are modulated by behaviour in the ferret but persist during both locomotion and immobility

Theta oscillations are a hallmark of hippocampal activity across mammals and play a critical role in many hippocampal models of memory and spatial navigation. To reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during auditory and visual localisation tasks designed to vary locomotion and sensory attention. Here, we show that theta oscillations occur during locomotion in both ferrets and rats, however during periods of immobility, theta oscillations persisted in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret was identified as analogous to Type 2 theta that has been observed in rodents due to its sensitivity to atropine, and was modulated by behavioural state, with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, differences exist between species in the relationship between theta and behavioural state.

neuroscience↗

Seasonal weight changes in laboratory ferrets

Ferrets (Mustela putorius furo) are a valuable animal model used in biomedical research. Ferrets undergo significant variation in body weight seasonally, affected by photoperiod, and these variations make it difficult to use weight as an indicator of health status. To overcome this requires a better understanding of these seasonal weight changes. We provide a normative weight data set for the female ferret accounting for seasonal changes, and also investigate the effect of fluid regulation on weight change. Female ferrets (n=39) underwent behavioural testing from May 2017 to August 2019 and were weighed daily while housed in an animal care facility with controlled light exposure. In the winter (October to March), animals experienced 10 hours of light and 14 hours of dark, while in summer (March to October), this contingency was reversed. Individual animals varied in their body weight from approximately 700 to 1200 g. However, weights fluctuated with light cycle, with animals losing weight in summer, and gaining weight in winter such that they fluctuated between approximately 80% and 120% of their long term average weight. Ferrets were weighed as part of their health assessment while experiencing water regulation for behavioural training. Water regulation superimposed additional weight changes on these seasonal fluctuations, with weight loss during the 5 day water regulation period being greater in summer than winter. These data establish a normative benchmark for seasonal weight variation in female ferrets that can be incorporated into the health assessment of an animals condition.

neuroscience↗

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

The ability to recognize sounds in noise is a key part of hearing, and the mechanisms by which the brain identifies sounds in noise are of considerable interest to scientists, clinicians and engineers. Yet we know little about the necessity of regions such as auditory cortex for hearing in noise, or how cortical processing of sounds is adversely affected by noise. Here we used reversible cortical inactivation and extracellular electrophysiology in ferrets performing a vowel discrimination task to identify and understand the causal contribution of auditory cortex to hearing in noise. Cortical inactivation by cooling impaired task performance in noisy but not clean conditions, while responses of auditory cortical neurons were less informative about vowel identity in noise. Simulations mimicking cortical inactivation indicated that effects of inactivation were related to the loss of information about sounds represented across neural populations. The addition of noise to target sounds drove spiking activity in auditory cortex and recruitment of additional neural populations that were linked to degraded behavioral performance. To suppress noise-related activity, we used continuous exposure to background noise to adapt the auditory system and recover behavioral performance in both ferrets and humans. Inactivation by cooling revealed that the benefits of continuous exposure were not cortically dependent. Together our results highlight the importance of auditory cortex in sound discrimination in noise and the underlying mechanisms through which noise-related activity and adaptation shape hearing.

neuroscience↗

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 ferrets 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.\n\nSignificance statementOur 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).

neuroscience↗

Egocentric and Allocentric Representations in Auditory Cortex

A key function of the brain is to provide a stable representation of an objects location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system and auditory cortex is necessary for sound localization. However the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects and here we recorded spatial receptive fields in auditory cortex freely moving ferrets. We found two distinct populations of neurons: While the majority ([~]80%) of spatially tuned neurons represented sound source location relative to the head, we provide novel evidence for a group of neurons in which space was represented in an allocentric world-centered coordinate frame. We also use our ability to measure spatial tuning in moving subjects to explore the influence of sound source distance and speed of head movements on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas for both populations modulation was stronger at faster movement speeds. Our findings argue that auditory cortex is involved in the representation of both sound source location relative to ourselves and sound location in the world independent of our own position.

neuroscience↗