Manuel S. Malmierca

Stimulus-Specific Adaptation in the Inferior Colliculus of the Anesthetized Rat

To identify sounds as novel, there must be some neural representation of commonly occurring sounds. Stimulus-specific adaptation (SSA) is a reduction in neural response to a repeated sound. Previous studies using an oddball stimulus paradigm have shown that SSA occurs at the cortex, but this study demonstrates that neurons in the inferior colliculus (IC) also show strong SSA using this paradigm. The majority (66%) of IC neurons showed some degree of SSA. Approximately 18% of neurons showed near-complete SSA. Neurons with SSA were found throughout the IC. Responses of IC neurons were reduced mainly during the onset component of the response, and latency was shorter in response to the oddball stimulus than to the standard. Neurons with near-complete SSA were broadly tuned to frequency, suggesting a high degree of convergence. Thus, some of the mechanisms that may underlie novelty detection and behavioral habituation to common sounds are already well developed at the midbrain.

Novelty detector neurons in the mammalian auditory midbrain.

Novel stimuli in all sensory modalities are highly effective in attracting and focusing attention. Stimulus‐specific adaptation (SSA) and brain activity evoked by novel stimuli have been studied using population measures such as imaging and event‐related potentials, but there have been few studies at the single‐neuron level. In this study we compare SSA across different populations of neurons in the inferior colliculus (IC) of the rat and show that a subclass of neurons with rapid and pronounced SSA respond selectively to novel sounds. These neurons, located in the dorsal and external cortex of the IC, fail to respond to multiple repetitions of a sound but briefly recover their excitability when some stimulus parameter is changed. The finding of neurons that respond selectively to novel stimuli in the mammalian auditory midbrain suggests that they may contribute to a rapid subcortical pathway for directing attention and/or orienting responses to novel sounds.

Iontophoresis in vivo demonstrates a key role for GABA(A) and glycinergic inhibition in shaping frequency response areas in the inferior colliculus of guinea pig.

The processing of biologically important sounds depends on the analysis of their frequency content by the cochlea and the CNS. GABAergic inhibition in the inferior colliculus shapes frequency response areas in echolocating bats, but a similar role in nonspecialized mammals has been questioned. We used the powerful combination of iontophoresis with detailed analysis of frequency response areas to test the hypothesis that GABAergic and glycinergic inhibition operating in the inferior colliculus of a nonspecialized mammal (guinea pig) shape the frequency responses of neurons in this nucleus. Our analysis reveals two groups of response areas in the inferior colliculus: V-shaped and non-V-shaped. The response as a function of level in neurons with V-shaped response areas can be either monotonic or nonmonotonic. Application of bicuculline or strychnine in these neurons, to block inhibition mediated by GABAA or glycinergic receptors, respectively, increases firing rate primarily within the boundaries of the control response area. In contrast, neurons in the non-V-shaped group have response areas that include narrow, closed, tilted, and double-peaked types. In this group, blockade of GABAA and glycine receptors increases firing rate but also changes response area shape, with most becoming more V-shaped. We conclude that (1) non-V-shaped response areas can be generated by GABA and glycinergic synapses within the inferior colliculus and do not simply reflect inhibition acting more peripherally in the pathway and (2) frequency-dependent inhibition is an important general feature of the mammalian inferior colliculus and not a specialization unique to echolocating bats.

Stimulus-Specific Adaptation in the Auditory Thalamus of the Anesthetized Rat

The specific adaptation of neuronal responses to a repeated stimulus (Stimulus-specific adaptation, SSA), which does not fully generalize to other stimuli, provides a mechanism for emphasizing rare and potentially interesting sensory events. Previous studies have demonstrated that neurons in the auditory cortex and inferior colliculus show SSA. However, the contribution of the medial geniculate body (MGB) and its main subdivisions to SSA and detection of rare sounds remains poorly characterized. We recorded from single neurons in the MGB of anaesthetized rats while presenting a sequence composed of a rare tone presented in the context of a common tone (oddball sequences). We demonstrate that a significant percentage of neurons in MGB adapt in a stimulus-specific manner. Neurons in the medial and dorsal subdivisions showed the strongest SSA, linking this property to the non-lemniscal pathway. Some neurons in the non-lemniscal regions showed strong SSA even under extreme testing conditions (e.g., a frequency interval of 0.14 octaves combined with a stimulus onset asynchrony of 2000 ms). Some of these neurons were able to discriminate between two very close frequencies (frequency interval of 0.057 octaves), revealing evidence of hyperacuity in neurons at a subcortical level. Thus, SSA is expressed strongly in the rat auditory thalamus and contribute significantly to auditory change detection.

A Discontinuous Tonotopic Organization in the Inferior Colliculus of the Rat

Audible frequencies of sound are encoded in a continuous manner along the length of the cochlea, and frequency is transmitted to the brain as a representation of place on the basilar membrane. The resulting tonotopic map has been assumed to be a continuous smooth progression from low to high frequency throughout the central auditory system. Here, physiological and anatomical data show that best frequency is represented in a discontinuous manner in the inferior colliculus, the major auditory structure of the midbrain. Multiunit maps demonstrate a distinct stepwise organization in the order of best frequency progression. Furthermore, independent data from single neurons show that best frequencies at octave intervals of approximately one-third are more prevalent than others. These data suggest that, in the inferior colliculus, there is a defined space of tissue devoted to a given frequency, and input within this frequency band may be pooled for higher-level processing.

The medial nucleus of the trapezoid body: comparative physiology.

Principal cells of the medial nucleus of the trapezoid body (MNTB) receive their excitatory input through large somatic terminals, the calyces of Held, which arise from axons of globular bushy cells located in the contralateral ventral cochlear nucleus. Discharges of MNTB neurons are characterized by high stimulus evoked firing rates, temporally precise onset responses, and a high degree of phase-locking to either pure tones or stimulus envelopes. Since the calyx of Held synapse is accessible to in vitro and to in vivo recordings, it serves as one of the most elaborate models for studying synaptic transmission in the mammalian brain. Although in such studies, the major emphasis is on synaptic physiology, the interpretation of the data will benefit from an understanding of the MNTBs contribution to auditory signal processing, including possible functional differences in different species. This implies the consideration of possible functional differences in different species. Here, we compare single unit recordings from MNTB principal cells in vivo in three different rodent species: gerbil, mouse and rat. Because of their good low-frequency hearing gerbils are often used in in vivo preparations, while mice and rats are predominantly used in slice preparations. We show that MNTB units in all three species exhibit high firing rates and precise onset-timing. Still there are species-specific specializations that might suggest the preferential use of one species over the others, depending on the scope of the respective investigation.

Effect of Auditory Cortex Deactivation on Stimulus-Specific Adaptation in the Medial Geniculate Body

An animals survival may depend on detecting new events or objects in its environment, and it is likely that the brain has evolved specific mechanisms to detect such changes. In sensory systems, neurons often exhibit stimulus-specific adaptation (SSA) whereby they adapt to frequently occurring stimuli, but resume firing when “surprised” by rare or new ones. In the auditory system, SSA has been identified in the midbrain, thalamus, and auditory cortex (AC). It has been proposed that the SSA observed subcortically originates in the AC as a higher-order property that is transmitted to the subcortical nuclei via corticofugal pathways. Here we report that SSA in the auditory thalamus of the rat remains intact when the AC is deactivated by cooling, thus demonstrating that the AC is not necessary for the generation of SSA in the thalamus. The AC does, however, modulate the responses of thalamic neurons in a way that strongly indicates a gain modulation mechanism. The changes imposed by the AC in thalamic neurons depend on the level of SSA that they exhibit.

The auditory novelty system: An attempt to integrate human and animal research

In this account, we attempt to integrate two parallel, but thus far, separate lines of research on auditory novelty detection: (1) human studies of EEG recordings of the mismatch negativity (MMN), and (2) animal studies of single-neuron recordings of stimulus-specific adaptation (SSA). The studies demonstrating the existence of novelty neurons showing SSA at different levels along the auditory pathways hierarchy, together with the recent results showing human auditory-evoked potential correlates of deviance detection at very short latencies, that is, at 20-40 ms from change onset, support the view that novelty detection is a key principle that governs the functional organization of the auditory system. Furthermore, the generation of the MMN recorded from the human scalp seems to involve a cascade of neuronal processing that occurs at different successive levels of the auditory systems hierarchy.

Laminar inputs from dorsal cochlear nucleus and ventral cochlear nucleus to the central nucleus of the inferior colliculus: two patterns of convergence.

The central nucleus of the inferior colliculus is a laminated structure composed of oriented dendrites and similarly oriented afferent fibers that provide a substrate for tonotopic organization. Although inputs from many sources converge in the inferior colliculus, how axons from these sources contribute to the laminar pattern has remained unclear. Here, we investigated the axons from the cochlear nuclei that terminate in the central nucleus of the cat and rat. After characterization of the best frequency of the neurons at the injection sites in the cochlear nucleus, the neurons were labeled with dextran in order to visualize their axons and synaptic boutons in the central nucleus. Quantitative methods were used to determine the size and distribution of the boutons within the laminar organization. Two components in the laminae were identified: (1) a narrow axonal lamina that included the largest fibers and largest boutons; (2) a wide axonal lamina, surrounding the narrow lamina, composed of thin fibers and only small boutons. The wide lamina was approximately 30-40% wider than the narrow lamina, and it often extended more than 100 microm beyond the larger boutons on each side. The presence of both thick and thin fibers within the acoustic striae following these injections suggests that large and small fibers/boutons within these bands may originate from different neuronal types in the dorsal and ventral cochlear nucleus. We conclude that the narrow laminae that contain large fibers and boutons originate from larger cell types in the cochlear nucleus. In contrast, the wide lamina composed exclusively of small boutons may represent an input from other, perhaps smaller neurons in the cochlear nucleus. Thus, two types of inferior colliculus laminar structures may originate from the cochlear nucleus, and the small boutons in the wide laminae may contribute a functionally distinct input to the neurons of the inferior colliculus.

The inferior colliculus of the rat : A quantitative analysis of monaural frequency response areas

Frequency response areas (FRAs) were measured for 237 single units in the inferior colliculus (IC) of urethane-anesthetized pigmented rats using monaural pure-tone stimulation. Based on qualitative criteria [J Neurosci 21 (2001) 7303], FRAs were classified as V-shaped in 69% of neurons, non-V-shaped in 29%, and unclassifiable in the remaining 2%. Non-V-shaped FRAs were heterogeneous, comprising a number of subtypes including narrow, closed, low- and high-tilt, multipeaked, U-shaped, mosaic and inhibitory. To complement this subjective classification, we applied quantitative measures used by others (e.g. [J Neurophysiol 84 (2000) 1012]), including the inverse slope of the upper and lower FRA borders, Q-values, and other measures of bandwidth. The results suggest that FRAs in the rat IC are best described as forming a continuous distribution among subtypes, rather than clustering into discrete categories. Moreover, there is a broad range of frequency tuning characteristics and FRA types across the entire frequency spectrum. Within this general pattern, however, there are some frequency-specific differences in FRA type distribution. The relative proportion of V-shaped FRAs was greatest at the high and low ends of the auditory range, with the highest proportion of non-V-shaped FRAs in the mid-range from 6 to 12 kHz. For most neurons with multipeaked FRAs, the peak frequencies were not harmonically related. Frequency tuning in the pigmented rat IC is generally similar to that in other species. Comparison of Q values across auditory nuclei shows little evidence that FRAs are sharpened at levels above the auditory nerve. Rather, there is a broad range of frequency tuning properties at each level.