Information processing by a sensory system is reflected in the changes in stimulus representation along its successive processing stages. We measured information content and stimulus-induced redundancy in the neural responses to a set of natural sounds in three successive stations of the auditory pathway-inferior colliculus (IC), auditory thalamus (MGB), and primary auditory cortex (A1). Information about stimulus identity was somewhat reduced in single A1 and MGB neurons relative to single IC neurons, when information is measured using spike counts, latency, or temporal spiking patterns. However, most of this difference was due to differences in firing rates. On the other hand, IC neurons were substantially more redundant than A1 and MGB neurons. IC redundancy was largely related to frequency selectivity. Redundancy reduction may be a generic organization principle of neural systems, allowing for easier readout of the identity of complex stimuli in A1 relative to IC.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca 2+ -impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

The responses of primary auditory cortex (A1) neurons to pure tones in anesthetized animals are usually described as having mostly narrow, unimodal frequency tuning and phasic responses. Thus A1 neurons are believed not to carry much information about pure tones beyond sound onset. In awake cats, however, tuning may be wider and responses may have substantially longer duration. Here we analyze frequency-response areas (FRAs) and temporal-response patterns of 1,828 units in A1 of halothane-anesthetized cats. Tuning was generally wide: the total bandwidth at 40 dB above threshold was 4 octaves on average. FRA shapes were highly variable and many were diffuse, not fitting into standard classification schemes. Analyzing the temporal patterns of the largest responses of each unit revealed that only 9% of the units had pure onset responses. About 40% of the units had sustained responses throughout stimulus duration (115 ms) and 13% of the units had significant and informative responses lasting 300 ms and more after stimulus offset. We conclude that under halothane anesthesia, neural responses show many of the characteristics of awake responses. Furthermore, A1 units maintain sensory information in their activity not only throughout sound presentation but also for hundreds of milliseconds after stimulus offset, thus possibly playing a role in sensory memory.

The responses of neurons to natural sounds and simplified natural sounds were recorded in the primary auditory cortex (AI) of halothane-anesthetized cats. Bird chirps were used as the base natural stimuli. They were first presented within the original acoustic context (at least 250 msec of sounds before and after each chirp). The first simplification step consisted of extracting a short segment containing just the chirp from the longer segment. For the second step, the chirp was cleaned of its accompanying background noise. Finally, each chirp was replaced by an artificial version that had approximately the same frequency trajectory but with constant amplitude. Neurons had a wide range of different response patterns to these stimuli, and many neurons had late response components in addition, or instead of, their onset responses. In general, every simplification step had a substantial influence on the responses. Neither the extracted chirp nor the clean chirp evoked a similar response to the chirp presented within its acoustic context. The extracted chirp evoked different responses than its clean version. The artificial chirps evoked stronger responses with a shorter latency than the corresponding clean chirp because of envelope differences. These results illustrate the sensitivity of neurons in AI to small perturbations of their acoustic input. In particular, they pose a challenge to models based on linear summation of energy within a spectrotemporal receptive field.

Animal vocalizations in natural settings are invariably accompanied by an acoustic background with a complex statistical structure. We have previously demonstrated that neuronal responses in primary auditory cortex of halothane-anesthetized cats depend strongly on the natural background. Here, we study in detail the neuronal responses to the background sounds and their relationships to the responses to the foreground sounds. Natural bird chirps as well as modifications of these chirps were used. The chirps were decomposed into three components: the clean chirps, their echoes, and the background noise. The last two were weaker than the clean chirp by 13 and 29 dB on average respectively. The test stimuli consisted of the full natural stimulus, the three basic components, and their three pairwise combinations. When the level of the background components (echoes and background noise) presented alone was sufficiently loud to evoke neuronal activity, these background components had an unexpectedly strong effect on the responses of the neurons to the main bird chirp. In particular, the responses to the original chirps were more similar on average to the responses evoked by the two background components than to the responses evoked by the clean chirp, both in terms of the evoked spike count and in terms of the temporal pattern of the responses. These results suggest that some of the neurons responded specifically to the acoustic background even when presented together with the substantially louder main chirp, and may imply that neurons in A1 already participate in auditory source segregation. Keywords: auditory cortex, cats, natural sounds, electrophysiology, single neurons INTRODUCTIONWhereas the representation of simple stimuli such as pure tones or amplitude-or frequency-modulated sounds in primary auditory cortex (A1) of mammals has been described in great detail (Bizley et al., 2005;Joris et al., 2004;Kadia and Wang, 2003;Liang et al., 2002;Moshitch et al., 2006;Nelken and Versnel, 2000;Read et al., 2002;Ricketts et al., 1998;Sutter and Loftus, 2003;Tan et al., 2004;Tian and Rauschecker, 1998;Tomita et al., 2004;Wehr and Zador, 2003), the processing of complex sounds, in particular natural sounds, in A1 is not well understood. Studies that have used natural sounds have shown that neurons in A1 are exquisitely sensitive to the detailed structure of complex sounds. In particular, one consistent finding (Creutzfeldt et al., 1980;Gehr et al., 2000;Machens et al., 2004;Pelleg-Toiba and Wollberg, 1991;Rotman et al., 2001;Sovijarvi, 1975;Wang et al., 1995) is that although the best frequency (BF) and the frequency response area (FRA) of a neuron are important determinants of its responses to a sound, individual neurons may respond idiosyncratically to different sounds.Thus, in the awake squirrel monkey, Pelleg-Toiba and Wollberg (1991) found that only in 2% of the neurons the responses to species-specific calls and time reversed calls ("llacs") were mirror image of each other, * Correspondence: Israel Nelken, Department ...