Exposure to 1800 MHz LTE electromagnetic fields under proinflammatory conditions decreases the response strength and increases the acoustic threshold of auditory cortical neurons.

Increased needs for mobile phone communications have raised successive generations (G) of wireless technologies, which could differentially affect biological systems. To test this, we exposed rats to single head-only exposure of a 4G long-term evolution (LTE)-1800 MHz electromagnetic field (EMF) for 2 h. We then assessed the impact on microglial space coverage and electrophysiological neuronal activity in the primary auditory cortex (ACx), under acute neuroinflammation induced by lipopolysaccharide. The mean specific absorption rate in the ACx was 0.5 W/kg. Multiunit recording revealed that LTE-EMF triggered reduction in the response strength to pure tones and to natural vocalizations, together with an increase in acoustic threshold in the low and medium frequencies. Iba1 immunohistochemistry showed no change in the area covered by microglia cell bodies and processes. In healthy rats, the same LTE-exposure induced no change in response strength and acoustic threshold. Our data indicate that acute neuroinflammation sensitizes neuronal responses to LTE-EMF, which leads to an altered processing of acoustic stimuli in the ACx.

Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds.

KEY POINTS: Enhancing cortical excitability can be achieved by either reducing intracortical inhibition or by enhancing intracortical excitation. Here we compare the consequences of reducing intracortical inhibition and of enhancing intracortical excitation on the processing of communication sounds in the primary auditory cortex. Local application of gabazine and of AMPA enlarged the spectrotemporal receptive fields and increased the responses to communication to the same extent. The Mutual Information (an index of the cortical neurons' ability to discriminate between natural sounds) was increased in both cases, as were the noise and signal correlations. Spike-timing reliability was only increased after gabazine application and post-excitation suppression was affected in the opposite way: it was increased when reducing the intracortical inhibition but was eliminated by enhancing the excitation. A computational model suggests that these results can be explained by an additive effect vs. a multiplicative effect ABSTRACT: The level of excitability of cortical circuits is often viewed as one of the critical factors controlling perceptive performance. In theory, enhancing cortical excitability can be achieved either by reducing inhibitory currents or by increasing excitatory currents. Here, we evaluated whether reducing inhibitory currents or increasing excitatory currents in auditory cortex similarly affects the neurons' ability to discriminate between communication sounds. We attenuated the inhibitory currents by application of gabazine (GBZ), and increased the excitatory currents by applying AMPA in the auditory cortex while testing frequency receptive fields and responses to communication sounds. GBZ and AMPA enlarged the receptive fields and increased the responses to communication sounds to the same extent. The spike-timing reliability of neuronal responses was largely increased when attenuating the intracortical inhibition but not after increasing the excitation. The discriminative abilities of cortical cells increased in both cases but this increase was more pronounced after attenuating the inhibition. The shape of the response to communication sounds was modified in the opposite direction: reducing inhibition increased post-excitation suppression whereas this suppression tended to disappear when increasing the excitation. A computational model indicates that the additive effect promoted by AMPA vs. the multiplicative effect of GBZ on neuronal responses, together with the dynamics of spontaneous cortical activity, can explain these differences. Thus, although apparently equivalent for increasing cortical excitability, acting on inhibition vs. on excitation impacts differently the cortical ability to discriminate natural stimuli, and only modulating inhibition changed efficiently the cortical representation of communication sounds.

Complexity of frequency receptive fields predicts tonotopic variability across species.

Primary cortical areas contain maps of sensory features, including sound frequency in primary auditory cortex (A1). Two-photon calcium imaging in mice has confirmed the presence of these global tonotopic maps, while uncovering an unexpected local variability in the stimulus preferences of individual neurons in A1 and other primary regions. Here we show that local heterogeneity of frequency preferences is not unique to rodents. Using two-photon calcium imaging in layers 2/3, we found that local variance in frequency preferences is equivalent in ferrets and mice. Neurons with multipeaked frequency tuning are less spatially organized than those tuned to a single frequency in both species. Furthermore, we show that microelectrode recordings may describe a smoother tonotopic arrangement due to a sampling bias towards neurons with simple frequency tuning. These results help explain previous inconsistencies in cortical topography across species and recording techniques.

Are there "local hotspots?" When concepts of cognitive psychology do not fit with physiological results.

Mather and colleagues' arguments require rethinking at the mechanistic level. The arguments on the physiological effects of norepinephrine at the cortical level are inconsistent with large parts of the literature. There is no evidence that norepinephrine induces local "hotspots": Norepinephrine mainly decreases evoked responses; facilitating effects are rare and not localized. More generally, the idea that perception benefits from "local hotspots" is hardly compatible with the fact that neural representations involve largely distributed activation of cortical and subcortical networks.

Stimulus-specific effects of noradrenaline in auditory cortex: implications for the discrimination of communication sounds.

KEY POINTS: Many studies have described the action of Noradrenaline (NA) on the properties of cortical receptive fields, but none has assessed how NA affects the discrimination abilities of cortical cells between natural stimuli. In the present study, we compared the consequences of NA topical application on spectro-temporal receptive fields (STRFs) and responses to communication sounds in the primary auditory cortex. NA application reduced the STRFs (an effect replicated by the alpha1 agonist Phenylephrine) but did not change, on average, the responses to communication sounds. For cells exhibiting increased evoked responses during NA application, the discrimination abilities were enhanced as quantified by Mutual Information. The changes induced by NA on parameters extracted from the STRFs and from responses to communication sounds were not related. ABSTRACT: The alterations exerted by neuromodulators on neuronal selectivity have been the topic of a vast literature in the visual, somatosensory, auditory and olfactory cortices. However, very few studies have investigated to what extent the effects observed when testing these functional properties with artificial stimuli can be transferred to responses evoked by natural stimuli. Here, we tested the effect of noradrenaline (NA) application on the responses to pure tones and communication sounds in the guinea-pig primary auditory cortex. When pure tones were used to assess the spectro-temporal receptive field (STRF) of cortical cells, NA triggered a transient reduction of the STRFs in both the spectral and the temporal domain, an effect replicated by the α1 agonist phenylephrine whereas α2 and ß agonists induced STRF expansion. When tested with communication sounds, NA application did not produce significant effects on the firing rate and spike timing reliability, despite the fact that α1, α2 and ß agonists by themselves had significant effects on these measures. However, the cells whose evoked responses were increased by NA application displayed enhanced discriminative abilities. These cells had initially smaller STRFs than the rest of the population. A principal component analysis revealed that the variations of parameters extracted from the STRF and those extracted from the responses to natural stimuli were not correlated. These results suggest that probing the action of neuromodulators on cortical cells with artificial stimuli does not allow us to predict their action on responses to natural stimuli.

A new and fast characterization of multiple encoding properties of auditory neurons.

The functional properties of auditory cortex neurons are most often investigated separately, through spectrotemporal receptive fields (STRFs) for the frequency tuning and the use of frequency sweeps sounds for selectivity to velocity and direction. In fact, auditory neurons are sensitive to a multidimensional space of acoustic parameters where spectral, temporal and spatial dimensions interact. We designed a multi-parameter stimulus, the random double sweep (RDS), composed of two uncorrelated random sweeps, which gives an easy, fast and simultaneous access to frequency tuning as well as frequency modulation sweep direction and velocity selectivity, frequency interactions and temporal properties of neurons. Reverse correlation techniques applied to recordings from the primary auditory cortex of guinea pigs and rats in response to RDS stimulation revealed the variety of temporal dynamics of acoustic patterns evoking an enhanced or suppressed firing rate. Group results on these two species revealed less frequent suppression areas in frequency tuning STRFs, the absence of downward sweep selectivity, and lower phase locking abilities in the auditory cortex of rats compared to guinea pigs.

Cortical inhibition reduces information redundancy at presentation of communication sounds in the primary auditory cortex.

In all sensory modalities, intracortical inhibition shapes the functional properties of cortical neurons but also influences the responses to natural stimuli. Studies performed in various species have revealed that auditory cortex neurons respond to conspecific vocalizations by temporal spike patterns displaying a high trial-to-trial reliability, which might result from precise timing between excitation and inhibition. Studying the guinea pig auditory cortex, we show that partial blockage of GABAA receptors by gabazine (GBZ) application (10 µm, a concentration that promotes expansion of cortical receptive fields) increased the evoked firing rate and the spike-timing reliability during presentation of communication sounds (conspecific and heterospecific vocalizations), whereas GABAB receptor antagonists [10 µm saclofen; 10-50 µm CGP55845 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid)] had nonsignificant effects. Computing mutual information (MI) from the responses to vocalizations using either the evoked firing rate or the temporal spike patterns revealed that GBZ application increased the MI derived from the activity of single cortical site but did not change the MI derived from population activity. In addition, quantification of information redundancy showed that GBZ significantly increased redundancy at the population level. This result suggests that a potential role of intracortical inhibition is to reduce information redundancy during the processing of natural stimuli.

How do auditory cortex neurons represent communication sounds?

A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

Component analysis reveals sharp tuning of the local field potential in the guinea pig auditory cortex.

Local field potentials (LFPs) recorded in the auditory cortex of mammals are known to reveal weakly selective and often multimodal spectrotemporal receptive fields in contrast to spiking activity. This may in part reflect the wider "listening sphere" of LFPs relative to spikes due to the greater current spread at low than high frequencies. We recorded LFPs and spikes from auditory cortex of guinea pigs using 16-channel electrode arrays. LFPs were processed by a component analysis technique that produces optimally tuned linear combinations of electrode signals. Linear combinations of LFPs were found to have sharply tuned responses, closer to spike-related tuning. The existence of a sharply tuned component implies that a cortical neuron (or group of neurons) capable of forming a linear combination of its inputs has access to that information. Linear combinations of signals from electrode arrays reveal information latent in the subspace spanned by multichannel LFP recordings and are justified by the fact that the observations themselves are linear combinations of neural sources.

How different are the local field potentials and spiking activities? Insights from multi-electrodes arrays.

Simultaneous recording of multiple neurons, or neuron groups, offers new promise for investigating fundamental questions about the neural code. We used arrays of 16 electrodes in the tonotopic, primary, auditory cortex of guinea pigs and we extracted LFP- and spike-based spectro-temporal receptive fields (STRFs). We confirm here that LFP signals provide broadly tuned activity which lacks frequency resolution compared to multiunit signals and, therefore, lead to large redundancy in neural responses even between recording sites far apart. Thanks to the use of multi-electrode arrays which allows simultaneous recordings, we also focused on functional relationships between neuronal discharges (through cross-correlations) and between LFPs (through coherence). Since the LFP is composed of distinct brain rhythms, the LFP results were split into three frequency bands from the slowest to the fastest components of LFPs. For driven as well as spontaneous activity, we show that components >70 Hz in LFPs are much less coherent between recording sites than slower components. In general, coherence between LFPs from two recordings sites is positively correlated with the degree of frequency overlap between the two corresponding STRFs, similar to cross-correlation between multiunit activities. However, coherence is only weakly correlated with cross-correlation in all frequency ranges. Altogether, these results suggest that LFPs reflect global functional connectivity in the thalamocortical auditory system whereas spiking activities reflect more independent local processing.