Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging.

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

Distinct Anatomical Connectivity Patterns Differentiate Subdivisions of the Nonlemniscal Auditory Thalamus in Mice.

Systematic examination of the inputs and outputs of the nonlemniscal auditory thalamus will facilitate the functional elucidation of this complex structure in the central auditory system. In mice, comprehensive tracing studies that reveal the long-range connectivity of the nonlemniscal auditory thalamus are lacking. To this end, we used Cre-inducible anterograde and monosynaptic retrograde viruses in Calbindin-2A-dgCre-D and Calretinin-IRES-Cre mice, focusing on the differences across subdivisions of the nonlemniscal auditory thalamus. We found that, 1) the dorsal and medial parts of the auditory thalamus were predominantly connected to sensory processing centers, whereas the posterior intralaminar (PIN) and peripeduncular nucleus (PP) were additionally connected to emotion and motivation modulation centers; 2) ventral auditory cortical areas were the major source of cortical inputs for all subdivisions, and the PIN/PP received more inputs from cortical layer 5 than other subdivisions did; 3) deep layers of the superior colliculus and rostral part of the nonlemniscal inferior colliculus preferentially projected to the PIN/PP; and 4) compared with the dorsal auditory thalamus, the PIN/PP mainly innervated association cortices. In addition, new brain areas connected to the nonlemniscal auditory thalamus, mostly the PIN/PP, were identified. Our results suggested subdivision-specific function of the nonlemniscal auditory thalamus in sound processing.

Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret.

A major challenge in neuroscience is to longitudinally monitor whole brain activity across multiple spatial scales in the same animal. Functional UltraSound (fUS) is an emerging technology that offers images of cerebral blood volume over large brain portions. Here we show for the first time its capability to resolve the functional organization of sensory systems at multiple scales in awake animals, both within small structures by precisely mapping and differentiating sensory responses, and between structures by elucidating the connectivity scheme of top-down projections. We demonstrate that fUS provides stable (over days), yet rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake ferrets, thus revealing its unprecedented functional resolution (100/300µm). This was performed in four different brain regions, including very small (1-2 mm3 size), deeply situated subcortical (8 mm deep) and previously undescribed structures in the ferret. Furthermore, we used fUS to map long-distance projections from frontal cortex, a key source of sensory response modulation, to auditory cortex.

Keeping track of sound objects in space: The contribution of early-stage auditory areas.

The influential dual-stream model of auditory processing stipulates that information pertaining to the meaning and to the position of a given sound object is processed in parallel along two distinct pathways, the ventral and dorsal auditory streams. Functional independence of the two processing pathways is well documented by conscious experience of patients with focal hemispheric lesions. On the other hand there is growing evidence that the meaning and the position of a sound are combined early in the processing pathway, possibly already at the level of early-stage auditory areas. Here, we investigated how early auditory areas integrate sound object meaning and space (simulated by interaural time differences) using a repetition suppression fMRI paradigm at 7 T. Subjects listen passively to environmental sounds presented in blocks of repetitions of the same sound object (same category) or different sounds objects (different categories), perceived either in the left or right space (no change within block) or shifted left-to-right or right-to-left halfway in the block (change within block). Environmental sounds activated bilaterally the superior temporal gyrus, middle temporal gyrus, inferior frontal gyrus, and right precentral cortex. Repetitions suppression effects were measured within bilateral early-stage auditory areas in the lateral portion of the Heschl's gyrus and posterior superior temporal plane. Left lateral early-stages areas showed significant effects for position and change, interactions Category x Initial Position and Category x Change in Position, while right lateral areas showed main effect of category and interaction Category x Change in Position. The combined evidence from our study and from previous studies speaks in favour of a position-linked representation of sound objects, which is independent from semantic encoding within the ventral stream and from spatial encoding within the dorsal stream. We argue for a third auditory stream, which has its origin in lateral belt areas and tracks sound objects across space.

The cat's meow: A high-field fMRI assessment of cortical activity in response to vocalizations and complex auditory stimuli.

Sensory systems are typically constructed in a hierarchical fashion such that lower level subcortical and cortical areas process basic stimulus features, while higher level areas reassemble these features into object-level representations. A number of anatomical pathway tracing studies have suggested that the auditory cortical hierarchy of the cat extends from a core region, consisting of the primary auditory cortex (A1) and the anterior auditory field (AAF), to higher level auditory fields that are located ventrally. Unfortunately, limitations on electrophysiological examination of these higher level fields have resulted in an incomplete understanding of the functional organization of the auditory cortex. Thus, the current study uses functional MRI in conjunction with a variety of simple and complex auditory stimuli to provide the first comprehensive examination of function across the entire cortical hierarchy. Auditory cortex function is shown to be largely lateralized to the left hemisphere, and is concentrated bilaterally in fields surrounding the posterior ectosylvian sulcus. The use of narrowband noise stimuli enables the visualization of tonotopic gradients in the posterior auditory field (PAF) and ventral posterior auditory field (VPAF) that have previously been unverifiable using fMRI and pure tones. Furthermore, auditory fields that are inaccessible to more invasive techniques, such as the insular (IN) and temporal (T) cortices, are shown to be selectively responsive to vocalizations. Collectively, these data provide a much needed functional correlate for anatomical examinations of the hierarchy of cortical structures within the cat auditory cortex.

Treefrogs as animal models for research on auditory scene analysis and the cocktail party problem.

The perceptual analysis of acoustic scenes involves binding together sounds from the same source and separating them from other sounds in the environment. In large social groups, listeners experience increased difficulty performing these tasks due to high noise levels and interference from the concurrent signals of multiple individuals. While a substantial body of literature on these issues pertains to human hearing and speech communication, few studies have investigated how nonhuman animals may be evolutionarily adapted to solve biologically analogous communication problems. Here, I review recent and ongoing work aimed at testing hypotheses about perceptual mechanisms that enable treefrogs in the genus Hyla to communicate vocally in noisy, multi-source social environments. After briefly introducing the genus and the methods used to study hearing in frogs, I outline several functional constraints on communication posed by the acoustic environment of breeding "choruses". Then, I review studies of sound source perception aimed at uncovering how treefrog listeners may be adapted to cope with these constraints. Specifically, this review covers research on the acoustic cues used in sequential and simultaneous auditory grouping, spatial release from masking, and dip listening. Throughout the paper, I attempt to illustrate how broad-scale, comparative studies of carefully considered animal models may ultimately reveal an evolutionary diversity of underlying mechanisms for solving cocktail-party-like problems in communication.

Thalamic and parietal brain morphology predicts auditory category learning.

Auditory categorization is a vital skill involving the attribution of meaning to acoustic events, engaging domain-specific (i.e., auditory) as well as domain-general (e.g., executive) brain networks. A listener's ability to categorize novel acoustic stimuli should therefore depend on both, with the domain-general network being particularly relevant for adaptively changing listening strategies and directing attention to relevant acoustic cues. Here we assessed adaptive listening behavior, using complex acoustic stimuli with an initially salient (but later degraded) spectral cue and a secondary, duration cue that remained nondegraded. We employed voxel-based morphometry (VBM) to identify cortical and subcortical brain structures whose individual neuroanatomy predicted task performance and the ability to optimally switch to making use of temporal cues after spectral degradation. Behavioral listening strategies were assessed by logistic regression and revealed mainly strategy switches in the expected direction, with considerable individual differences. Gray-matter probability in the left inferior parietal lobule (BA 40) and left precentral gyrus was predictive of "optimal" strategy switch, while gray-matter probability in thalamic areas, comprising the medial geniculate body, co-varied with overall performance. Taken together, our findings suggest that successful auditory categorization relies on domain-specific neural circuits in the ascending auditory pathway, while adaptive listening behavior depends more on brain structure in parietal cortex, enabling the (re)direction of attention to salient stimulus properties.

Maps of ITD in the nucleus laminaris of the barn owl.

Axons from the nucleus magnocellularis (NM) and their targets in nucleus laminaris (NL) form the circuit responsible for encoding interaural time differences (ITDs). In barn owls, NL receives bilateral inputs from NM such that axons from the ipsilateral NM enter NL dorsally, while contralateral axons enter from the ventral side. These afferents and their synapses on NL neurons generate a tone-induced local field potential, or neurophonic, that varies systematically with position in NL. From dorsal to ventral within the nucleus, the best interaural time difference (ITD) of the neurophonic shifts from contralateral space to best ITDs around 0 µs. Earlier recordings suggested that in NL, iso-delay contours ran parallel to the dorsal and ventral borders of NL (Sullivan WE, Konishi M. Proc Natl Acad Sci U S A 83:8400-8404, 1986). This axis is orthogonal to that seen in chicken NL, where a single map of ITD runs from around 0 µs ITD medially to contralateral space laterally (Köppl C, Carr CE. Biol Cyber 98:541-559, 2008). Yet the trajectories of the NM axons are similar in owl and chicken (Seidl AH, Rubel EW, Harris DM, J Neurosci 30:70-80, 2010). We therefore used clicks to measure conduction time in NL and made lesions to mark the 0 µs iso-delay contour in multiple penetrations along an isofrequency slab. Iso-delay contours were not parallel to the dorsal and ventral borders of NL; instead the 0 µs iso-delay contour shifted systematically from a dorsal position in medial NL to a ventral position in lateral NL. Could different conduction delays account for the mediolateral shift in the representation of 0 µs ITD? We measured conduction delays using the neurophonic potential and developed a simple linear model of the delay-line conduction velocity. We then raised young owls with time-delaying earplugs in one ear (Gold JI, Knudsen EI, J Neurophysiol 82:2197-2209, 1999) to examine map plasticity.

The generation of direction selectivity in the auditory system.

Both human speech and animal vocal signals contain frequency-modulated (FM) sounds. Although central auditory neurons that selectively respond to the direction of frequency modulation are known, the synaptic mechanisms underlying the generation of direction selectivity (DS) remain elusive. Here we show the emergence of DS neurons in the inferior colliculus by mapping the three major subcortical auditory nuclei. Cell-attached recordings reveal a highly reliable and precise firing of DS neurons to FM sweeps in a preferred direction. By using in vivo whole-cell current-clamp and voltage-clamp recordings, we found that the synaptic inputs to DS neurons are not direction selective, but temporally reversed excitatory and inhibitory synaptic inputs are evoked in response to opposing directions of FM sweeps. The construction of such temporal asymmetry, resulting DS, and its topography can be attributed to the spectral disparity of the excitatory and the inhibitory synaptic tonal receptive fields.

Auditory adaptation to sound intensity in conscious rats: 2-[F-18]-fluoro-2-deoxy-D-glucose PET study.

Despite the importance of the adaptive process for discriminating the broad range of sound intensity, there have been few systemic investigations targeting the auditory mechanisms. In this study, the adaptation effect of sound intensity on the change in glucose metabolism in rat brains was examined using a PET technique. In the first experiment, broadband white noise sound (40, 60, 80, or 100 dB sound pressure level) was given for 30 min after an 2-[F-18]-fluoro-2-deoxy-D-glucose injection in an awake condition. In the second experiment, sound stimuli with an intensity modulation of 0, 0.5, and 5.0 Hz in frequency and at three intensity levels were used for examining the metabolism change according to the short time scale variation of the sound intensity. As a result, the metabolic activities in the bilateral cochlear nucleus, superior olivary complexes, and inferior colliculus were proportional to the sound intensity level, whereas the bilateral auditory cortical areas unexpectedly decreased as the sound intensity level increased in the first experiment. In the second experiment, the glucose metabolism in the auditory cortex was higher at 0.5 and 5.0 Hz modulation frequency than the 0.0 Hz modulation frequency, while retaining an inverse relationship with the sound intensity. The metabolism in inferior colliculus was higher at 5.0 Hz modulation frequency than 0.0 and 0.5 Hz modulation frequencies. Taken together, the auditory cortex metabolism seemed to be actively adapted to the average sound intensity, which indicates that it plays an important role in processing the broad range to sound intensity more than the other nucleus of the auditory pathway. Especially, this study demonstrated that the sound intensity-dependent glucose metabolism can be seen in a small rodent's brain stem level using 2-[F-18]-fluoro-2-deoxy-D-glucose PET functional neuroimaging.

Thalamocortical projections to rat auditory cortex from the ventral and dorsal divisions of the medial geniculate nucleus.

The ventral and dorsal medial geniculate (MGV and MGD) constitute the major auditory thalamic subdivisions providing thalamocortical inputs to layer IV and lower layer III of auditory cortex. No quantitative evaluation of this projection is available. Using biotinylated dextran amine (BDA)/biocytin injections, we describe the cortical projection patterns of MGV and MGD cells. In primary auditory cortex the bulk of MGV axon terminals are in layer IV/lower layer III with minor projections to supragranular layers and intermediate levels in infragranular layers. MGD axons project to cortical regions designated posterodorsal (PD) and ventral (VA) showing laminar terminal distributions that are quantitatively similar to the MGV-to-primary cortex terminal distribution. At the electron microscopic level MGV and MGD terminals are non-γ-aminobutyric acid (GABA)ergic with MGD terminals in PD and VA slightly but significantly larger than MGV terminals in primary cortex. MGV/MGD terminals synapse primarily onto non-GABAergic spines/dendrites. A small number synapse on GABAergic structures, contacting large dendrites or cell bodies primarily in the major thalamocortical recipient layers. For MGV projections to primary cortex or MGD projections to PD or VA, the non-GABAergic postsynaptic structures at each site were the same size regardless of whether they were in supragranular, granular, or infragranular layers. However, the population of MGD terminal-recipient structures in VA were significantly larger than the MGD terminal-recipient structures in PD or the MGV terminal-recipient structures in primary cortex. Thus, if terminal and postsynaptic structure size indicate strength of excitation then MGD to VA inputs are strongest, MGD to PD intermediate, and MGV to primary cortex the weakest.

Neurochemical organization and experience-dependent activation of estrogen-associated circuits in the songbird auditory forebrain.

The classic steroid hormone estradiol is rapidly produced by central auditory neurons in the songbird brain and instantaneously modulates auditory coding to enhance the neural and behavioral discrimination of acoustic signals. Although recent advances highlight novel roles for estradiol in the regulation of central auditory processing, current knowledge on the functional and neurochemical organization of estrogen-associated circuits, as well as the impact of sensory experience in these auditory forebrain networks, remains very limited. Here we show that both estrogen-producing and -sensitive neurons are highly expressed in the caudomedial nidopallium (NCM), the zebra finch analog of the mammalian auditory association cortex, but not other auditory forebrain areas. We further demonstrate that auditory experience primarily engages estrogen-producing, and to a lesser extent, estrogen-responsive neurons in NCM, that these neuronal populations moderately overlap and that acute episodes of sensory experience do not quantitatively affect these circuits. Finally, we show that whereas estrogen-producing cells are neurochemically heterogeneous, estrogen-sensitive neurons are primarily glutamatergic. These findings reveal the neurochemical and functional organization of estrogen-associated circuits in the auditory forebrain, demonstrate their activation and stability in response to sensory experience in behaving animals, and highlight estrogenic circuits as fundamental components of central networks supporting sensory processing.

Thalamocortical pathway specialization for sound frequency resolution.

Core auditory cortices are organized in parallel pathways that process incoming sensory information differently. In the rat, sound filtering properties of the primary (A1) and ventral (VAF) auditory fields are markedly different, yet both are core regions that by definition receive most of their thalamic input from the ventral nucleus (MGBv) of the medial geniculate body (MGB). For example, spike rate responses to sound intensity and frequency are more narrowly resolved in VAF vs. A1. Here we question whether there are anatomic correlates of the marked differences in response properties in these two core auditory fields. Combined Fourier optical imaging and multiunit recording methods were used to map tone frequency responses with high spatial resolution in A1, VAF, and neighboring cortices. The cortical distance representing a given octave was similar, yet response frequency resolution was about twice as large in VAF as in A1. Retrograde tracers were injected into low- and high-isofrequency contours of both regions to compare MGBv label patterns. The distance between clusters of MGBv neurons projecting to low- and high-isofrequency contours in the cortex was twice as large in caudal as in rostral MGB. This suggests that differences in A1 and VAF frequency resolution are related to the anatomic spatial resolution of frequency laminae in the thalamus, supporting a growing consensus that antecedents of cortical specialization can be attributed in part to the structural and functional characteristics of thalamocortical inputs.

Topography and morphology of the inhibitory projection from superior olivary nucleus to nucleus laminaris in chickens (Gallus gallus).

The avian nucleus laminaris (NL) is involved in computation of interaural time differences (ITDs) that encode the azimuthal position of a sound source. Neurons in NL are bipolar, with dorsal and ventral dendritic arbors receiving input from separate ears. NL neurons act as coincidence detectors that respond maximally when input from each ear arrives at the two dendritic arbors simultaneously. Computational and physiological studies demonstrated that the sensitivity of NL neurons to coincident inputs is modulated by an inhibitory feedback circuit via the superior olivary nucleus (SON). To understand the mechanism of this modulation, the topography of the projection from SON to NL was mapped, and the morphology of the axon terminals of SON neurons in NL was examined in chickens (Gallus gallus). In vivo injection of AlexaFluor 568 dextran amine into SON demonstrated a coarse topographic projection from SON to NL. Retrogradely labeled neurons in NL were located within the zone of anterogradely labeled terminals, suggesting a reciprocal projection between SON to NL. In vivo extracellular physiological recording further demonstrated that this topography is consistent with tonotopic maps in SON and NL. In addition, three-dimensional reconstruction of single SON axon branches within NL revealed that individual SON neurons innervate a large area of NL and terminate on both dorsal and ventral dendritic arbors of NL neurons. The organization of the projection from SON to NL supports its proposed functions of controlling the overall activity level of NL and enhancing the specificity of frequency mapping and ITD detection.

Information flow in the auditory cortical network.

Auditory processing in the cerebral cortex is comprised of an interconnected network of auditory and auditory-related areas distributed throughout the forebrain. The nexus of auditory activity is located in temporal cortex among several specialized areas, or fields, that receive dense inputs from the medial geniculate complex. These areas are collectively referred to as auditory cortex. Auditory activity is extended beyond auditory cortex via connections with auditory-related areas elsewhere in the cortex. Within this network, information flows between areas to and from countless targets, but in a manner that is characterized by orderly regional, areal and laminar patterns. These patterns reflect some of the structural constraints that passively govern the flow of information at all levels of the network. In addition, the exchange of information within these circuits is dynamically regulated by intrinsic neurochemical properties of projecting neurons and their targets. This article begins with an overview of the principal circuits and how each is related to information flow along major axes of the network. The discussion then turns to a description of neurochemical gradients along these axes, highlighting recent work on glutamate transporters in the thalamocortical projections to auditory cortex. The article concludes with a brief discussion of relevant neurophysiological findings as they relate to structural gradients in the network.

Fast propagating waves within the rodent auditory cortex.

Central processing of acoustic signals is assumed to take place in a stereotypical spatial and temporal pattern involving different fields of auditory cortex. So far, cortical propagating waves representing such patterns have mainly been demonstrated by optical imaging, repeatedly in the visual and somatosensory cortex. In this study, the surface of rat auditory cortex was mapped by recording local field potentials (LFPs) in response to a broadband acoustic stimulus. From the peak amplitudes of LFPs, cortical activation maps were constructed over 4 cortical auditory fields. Whereas response onset had same latencies across primary auditory field (A1), anterior auditory field (AAF), and ventral auditory field and longer latencies in posterior auditory field, activation maps revealed a reproducible wavelike pattern of activity propagating for ∼45 ms poststimulus through all cortical fields. The movement observed started with 2 waves within the primary auditory fields A1 and AAF moving from ventral to dorsal followed by a motion from rostral to caudal, passing continuously through higher-order fields. The pattern of propagating waves was well reproducible and showed only minor changes if different anesthetics were used. The results question the classical "hierarchical" model of cortical areas and demonstrate that the different fields process incoming information as a functional unit.

Differential patterns of inputs create functional zones in central nucleus of inferior colliculus.

Distinct pathways carry monaural and binaural information from the lower auditory brainstem to the central nucleus of the inferior colliculus (ICC). Previous anatomical and physiological studies suggest that differential ascending inputs to regions of the ICC create functionally distinct zones. Here, we provide direct evidence of this relationship by combining recordings of single unit responses to sound in the ICC with focal, iontophoretic injections of the retrograde tracer Fluoro-Gold at the physiologically characterized sites. Three main patterns of anatomical inputs were observed. One pattern was identified by inputs from the cochlear nucleus and ventral nucleus of the lateral lemniscus in isolation, and these injection sites were correlated with monaural responses. The second pattern had inputs only from the ipsilateral medial and lateral superior olive, and these sites were correlated with interaural time difference (ITD)-sensitive responses to low frequency (<500 Hz). A third pattern had inputs from a variety of olivary and lemniscal sources, notably the contralateral lateral superior olive and dorsal nucleus of the lateral lemniscus. These were correlated with high-frequency ITD sensitivity to complex acoustic stimuli. These data support the notion of anatomical regions formed by specific patterns of anatomical inputs to the ICC. Such synaptic domains may represent functional zones in ICC.

Frequency processing at consecutive levels in the auditory system of bush crickets (tettigoniidae).

We asked how processing of male signals in the auditory pathway of the bush cricket Ancistrura nigrovittata (Phaneropterinae, Tettigoniidae) changes from the ear to the brain. From 37 sensory neurons in the crista acustica single elements (cells 8 or 9) have frequency tuning corresponding closely to the behavioral tuning of the females. Nevertheless, one-quarter of sensory neurons (approximately cells 9 to 18) excite the ascending neuron 1 (AN1), which is best tuned to the male's song carrier frequency. AN1 receives frequency-dependent inhibition, reducing sensitivity especially in the ultrasound. When recorded in the brain, AN1 shows slightly lower overall activity than when recorded in the prothoracic ganglion close to the spike-generating zone. This difference is significant in the ultrasonic range. The first identified local brain neuron in a bush cricket (LBN1) is described. Its dendrites overlap with some of AN1-terminations in the brain. Its frequency tuning and intensity dependence strongly suggest a direct postsynaptic connection to AN1. Spiking in LBN1 is only elicited after summation of excitatory postsynaptic potentials evoked by individual AN1-action potentials. This serves a filtering mechanism that reduces the sensitivity of LBN1 and also its responsiveness to ultrasound as compared to AN1. Consequently, spike latencies of LBN1 are long (>30 ms) despite its being a second-order interneuron. Additionally, LBN1 receives frequency-specific inhibition, most likely further reducing its responses to ultrasound. This demonstrates that frequency-specific inhibition is redundant in two directly connected interneurons on subsequent levels in the auditory system.

Thalamic label patterns suggest primary and ventral auditory fields are distinct core regions.

A hierarchical scheme proposed by Kaas and colleagues suggests that primate auditory cortex can be divided into core and belt regions based on anatomic connections with thalamus and distinctions among response properties. According to their model, core auditory cortex receives predominantly unimodal sensory input from the ventral nucleus of the medial geniculate body (MGBv); whereas belt cortex receives predominantly cross-modal sensory input from nuclei outside the MGBv. We previously characterized distinct response properties in rat primary (A1) versus ventral auditory field (VAF) cortex; however, it has been unclear whether VAF should be categorized as a core or belt auditory cortex. The current study employed high-resolution functional imaging to map intrinsic metabolic responses to tones and to guide retrograde tracer injections into A1 and VAF. The size and density of retrogradely labeled somas in the medial geniculate body (MGB) were examined as a function of their position along the caudal-to-rostral axis, subdivision of origin, and cortical projection target. A1 and VAF projecting neurons were found in the same subdivisions of the MGB but in rostral and caudal parts, respectively. Less than 3% of the cells projected to both regions. VAF projecting neurons were smaller than A1 projecting neurons located in dorsal (MGBd) and suprageniculate (SG) nuclei. Thus, soma size varied with both caudal-rostral position and cortical target. Finally, the majority (>70%) of A1 and VAF projecting neurons were located in MGBv. These MGB connection profiles suggest that rat auditory cortex, like primate auditory cortex, is made up of multiple distinct core regions.

Smelling sounds: olfactory-auditory sensory convergence in the olfactory tubercle.

Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not understood. Here, we report novel findings revealing that the early olfactory code is subjected to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single units selectively respond to odors-with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single units also showed robust responses to an auditory tone. Furthermore, 29% of single units tested displayed supraadditive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation nor modulation of odor-evoked activity by tone-suggesting a lack of olfactory-auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing and may serve as a seat for psychophysical interactions between smells and sounds.