Evidence of a Functionally Segregated Pathway from Dorsal Cochlear Nucleus to Inferior Colliculus

Journal of Neurophysiology. Apr, 2002  |  Pubmed ID: 11929904

Type O units in the central nucleus of the inferior colliculus (ICC) of decerebrate cats are excited by best frequency (BF) tones near threshold, but are inhibited by high-level tones at all frequencies. Dorsal cochlear nucleus (DCN) principal cells display similar response map features and project directly to the ICC, and are thus supposed to be the dominant source of excitatory input for type O units. To test this hypothesis, the responses of type O units were compared before and after two pharmacological manipulations. When DCN to ICC axons were blocked by pressure injections of lidocaine, most type O units (approximately 80%) were silenced or showed substantially reduced activity, but some units showed increased activity. All of the former units had low maximal rates to BF tones, whereas the latter units had high rates. When local circuit inhibitory mechanisms in the ICC were blocked by iontophoretic application of bicuculline or strychnine, type O unit responses also fell into two classes: low-rate units that showed increased spontaneous and driven activities and high-rate units that showed, in addition, altered response map features. Taken together, these results demonstrate that low-rate type O units are part of a functionally segregated pathway initiated by the DCN, whereas high-rate type O units are created at the level of the ICC.

Auditory Processing of Spectral Cues for Sound Localization in the Inferior Colliculus

Journal of the Association for Research in Otolaryngology : JARO. Jun, 2003  |  Pubmed ID: 12943370

The head-related transfer function (HRTF) of the cat adds directionally dependent energy minima to the amplitude spectrum of complex sounds. These spectral notches are a principal cue for the localization of sound source elevation. Physiological evidence suggests that the dorsal cochlear nucleus (DCN) plays a critical role in the brainstem processing of this directional feature. Type O units in the central nucleus of the inferior colliculus (ICC) are a primary target of ascending DCN projections and, therefore, may represent midbrain specializations for the auditory processing of spectral cues for sound localization. Behavioral studies confirm a loss of sound orientation accuracy when DCN projections to the inferior colliculus are surgically lesioned. This study used simple analogs of HRTF notches to characterize single-unit response patterns in the ICC of decerebrate cats that may contribute to the directional sensitivity of the brain's spectral processing pathways. Manipulations of notch frequency and bandwidth demonstrated frequency-specific excitatory responses that have the capacity to encode HRTF-based cues for sound source location. These response patterns were limited to type O units in the ICC and have not been observed for the projection neurons of the DCN. The unique spectral integration properties of type O units suggest that DCN influences are transformed into a more selective representation of sound source location by a local convergence of wideband excitatory and frequency-tuned inhibitory inputs.

Decreased Cortical Gray and Cerebral White Matter in Male Patients with Familial Bipolar I Disorder

Journal of Affective Disorders. Nov, 2004  |  Pubmed ID: 15555701

Previous MRI studies of bipolar disorder have failed to consistently demonstrate cortical gray or cerebral white matter tissue loss, as well as sulcal or ventricular enlargement. The inconsistencies are most likely due to the clinical and gender heterogeneity of the study populations as well as the different MRI acquisition and processing techniques. The objective of this study was to determine if there was a cortical gray matter and cerebral white matter deficit as well as sulcal and ventricular enlargement in a homogeneous sample of euthymic male patients with familial bipolar I disorder.

Contralateral Effects and Binaural Interactions in Dorsal Cochlear Nucleus

Journal of the Association for Research in Otolaryngology : JARO. Sep, 2005  |  Pubmed ID: 16075189

The dorsal cochlear nucleus (DCN) receives afferent input from the auditory nerve and is thus usually thought of as a monaural nucleus, but it also receives inputs from the contralateral cochlear nucleus as well as descending projections from binaural nuclei. Evidence suggests that some of these commissural and efferent projections are excitatory, whereas others are inhibitory. The goals of this study were to investigate the nature and effects of these inputs in the DCN by measuring DCN principal cell (type IV unit) responses to a variety of contralateral monaural and binaural stimuli. As expected, the results of contralateral stimulation demonstrate a mixture of excitatory and inhibitory influences, although inhibitory effects predominate. Most type IV units are weakly, if at all, inhibited by tones but are strongly inhibited by broadband noise (BBN). The inhibition evoked by BBN is also low threshold and short latency. This inhibition is abolished and excitation is revealed when strychnine, a glycine-receptor antagonist, is applied to the DCN; application of bicuculline, a GABAA-receptor antagonist, has similar effects but does not block the onset of inhibition. Manipulations of discrete fiber bundles suggest that the inhibitory, but not excitatory, inputs to DCN principal cells enter the DCN via its output pathway, and that the short latency inhibition is carried by commissural axons. Consistent with their respective monaural effects, responses to binaural tones as a function of interaural level difference are essentially the same as responses to ipsilateral tones, whereas binaural BBN responses decrease with increasing contralateral level. In comparison to monaural responses, binaural responses to virtual space stimuli show enhanced sensitivity to the elevation of a sound source in ipsilateral space but reduced sensitivity in contralateral space. These results show that the contralateral inputs to the DCN are functionally relevant in natural listening conditions, and that one role of these inputs is to enhance DCN processing of spectral sound localization cues produced by the pinna.

Spectral Processing in the Inferior Colliculus

International Review of Neurobiology. 2005  |  Pubmed ID: 16472635

Response Properties of Single Units in the Dorsal Nucleus of the Lateral Lemniscus of Decerebrate Cats

Journal of Neurophysiology. Sep, 2007  |  Pubmed ID: 17652420

The dorsal nucleus of the lateral lemniscus (DNLL) receives afferent inputs from many brain stem nuclei and, in turn, is a major source of inhibitory inputs to the inferior colliculus (IC). The goal of this study was to characterize the monaural and binaural response properties of neurons in the DNLL of unanesthetized decerebrate cat. Monaural responses were classified according to the patterns of excitation and inhibition observed in contralateral and ipsilateral frequency response maps. Binaural classification was based on unit sensitivity to interaural level differences. The results show that units in the DNLL can be grouped into three distinct types. Type v units produce contralateral response maps that show a wide V-shaped excitatory area and no inhibition. These units receive ipsilateral excitation and exhibit binaural facilitation. The contralateral maps of type i units show a more restricted I-shaped region of excitation that is flanked by inhibition. Type o maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Both type i and type o units receive ipsilateral inhibition and exhibit binaural inhibition. Units that produce type v maps have a low best frequency (BF), whereas type i and type o units have high BFs. Type v and type i units give monotonic rate-level responses for both BF tones and broadband noise. Type o units are inhibited by tones at high levels, but are excited by high-level noise. These results show that the DNLL can exert strong, differential effects in the IC.

The Effects of Geometric and Threshold Definitions on Cortical Bone Metrics Assessed by in Vivo High-resolution Peripheral Quantitative Computed Tomography

Calcified Tissue International. Nov, 2007  |  Pubmed ID: 17952361

This study evaluates in vivo methods for calculating cortical thickness (Ct.Th) with respect to sensitivity to tissue-level changes in mineralization and the ability to predict whole-bone mechanical properties. Distal radial and tibial images obtained from normal volunteers using high-resolution peripheral quantitative computed tomography (HR-pQCT) were segmented using three thresholds including the manufacturer default and +/-5% in terms of equivalent mineral density. Ct.Th was determined in two ways: using a direct three-dimensional (3D) method and using an annular method, where cortical bone volume is divided by periosteal surface area. D(comp) (mg HA/cm(3)) was calculated based on the mean density-calibrated linear attenuation values of the cortical compartment. Finite element analysis was performed to evaluate the predictive ability of the annular and direct Ct.Th methods. Using the direct 3D method, a +/-5% change in threshold resulted in a 2% mean difference in Ct.Th for both the radius and tibia. An average difference of 5% was found using the annular method. The change in threshold produced changes in D(comp) ranging 0.50-1.56% for both the tibia and radius. Annular Ct.Th correlated more strongly with whole-bone apparent modulus (R(2)=0.64 vs. R(2)=0.41). Both thickness calculation methods and threshold selection have a direct impact on cortical parameters derived from HR-pQCT images. Indirectly, these results suggest that moderate changes in tissue-level mineralization can affect cortical measures. Furthermore, while the direct 3D Ct.Th method is less sensitive to threshold effects, both methods are moderate predictors of mechanical strength, with the annular method being the stronger correlate.

On the Role of the Wideband Inhibitor in the Dorsal Cochlear Nucleus: a Computational Modeling Study

Journal of the Association for Research in Otolaryngology : JARO. Dec, 2008  |  Pubmed ID: 18704579

Principal cells (type IV units) in the dorsal cochlear nucleus (DCN) are uniquely sensitive to (are inhibited by) energy minima or notches in acoustic spectra, which provide cues to sound localization. The once accepted conceptual model of the DCN suggested that this sensitivity was shaped largely by inhibitory inputs from wideband inhibitors (WBIs), which received auditory nerve inputs over a wide frequency range and inhibited type IV units over a narrow frequency range. A computational model based on this wide-input narrow-output conceptual model was able to reproduce quantitatively type IV unit responses to notch-noise stimuli as a function of notch width. Recent physiological results have shown however that WBIs are unresponsive to notch-noise stimuli with wide notch widths and thus have narrower auditory nerve fiber input bandwidths than previously assumed. A computational model based on a narrow-input narrow-output model of the WBI was unable to account fully for the notch sensitivity of type IV units suggesting the need to add a new component to the DCN circuit. The goal of this study was to test whether making the output bandwidth of the WBIs wide while keeping their input bandwidth narrow could explain the responses of type IV units to notch-noise stimuli. Anatomical evidence supports this model configuration, and the results show that such a model can produce strong inhibition in type IV units for wide notches. The results thus suggest that WBIs, in narrow-input wide-output form, are sufficient to account for the notch sensitivity of DCN type IV units.

Monaural Spectral Processing Differs Between the Lateral Superior Olive and the Inferior Colliculus: Physiological Evidence for an Acoustic Chiasm

Hearing Research. Oct, 2010  |  Pubmed ID: 20600738

Evidence suggests that the lateral superior olive (LSO) initiates an excitatory pathway specialized to process interaural level differences (ILDs), the primary cues used by mammals to localize high-frequency sounds in the horizontal plane. Type I units in the central nucleus of the inferior colliculus (ICC) of decerebrate cats exhibit monaural and binaural response properties qualitatively similar to those of LSO units, and are thus supposed to be the midbrain component of the ILD pathway. Studies have shown, however, that the responses of ICC cells do not often reflect simply the output of any single source of excitatory inputs. The goal of this study was to compare directly the monaural, spectral response properties of LSO and type I units measured in unanesthetized decerebrate cats. Compared to LSO units, type I units have narrower V-shaped excitatory tuning curves, higher spontaneous rates, lower maximum stimulus-evoked firing rates and more nonmonotonic rate-level curves for tones and noise. In addition, low-frequency type I units have lower thresholds to tones than corresponding LSO units. Taken together, these results suggest that the excitatory ILD pathway from LSO to ICC is mostly a high-frequency channel, and that additional inputs transform LSO influences in the ICC.

High-resolution Peripheral Quantitative Computed Tomographic Imaging of Cortical and Trabecular Bone Microarchitecture in Patients with Type 2 Diabetes Mellitus

The Journal of Clinical Endocrinology and Metabolism. Nov, 2010  |  Pubmed ID: 20719835

Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone mineral density (BMD).

Dynamic Cell Behavior on Shape Memory Polymer Substrates

Biomaterials. Mar, 2011  |  Pubmed ID: 21224032

Cell culture substrates of defined topography have emerged as powerful tools with which to investigate cell mechanobiology, but current technologies only allow passive control of substrate properties. Here we present a thermo-responsive cell culture system that uses shape memory polymer (SMP) substrates that are programmed to change surface topography during cell culture. Our hypothesis was that a shape-memory-activated change in substrate topography could be used to control cell behavior. To test this hypothesis, we embossed an initially flat SMP substrate to produce a temporary topography of parallel micron-scale grooves. After plating cells on the substrate, we triggered shape memory activation using a change in temperature tailored to be compatible with mammalian cell culture, thereby causing topographic transformation back to the original flat surface. We found that the programmed erasure of substrate topography caused a decrease in cell alignment as evidenced by an increase in angular dispersion with corresponding remodeling of the actin cytoskeleton. Cell viability remained greater than 95% before and after topography change and temperature increase. These results demonstrate control of cell behavior through shape-memory-activated topographic changes and introduce the use of active cell culture SMP substrates for investigation of mechanotransduction, cell biomechanical function, and cell soft-matter physics.

Somatosensory Context Alters Auditory Responses in the Cochlear Nucleus

Journal of Neurophysiology. Mar, 2011  |  Pubmed ID: 21178001

The cochlear nucleus, the first central auditory structure, performs initial stimulus processing and segregation of information into parallel ascending pathways. It also receives nonauditory inputs. Here we show in vivo that responses of dorsal cochlear nucleus (DCN) principal neurons to sounds can change significantly depending on the presence or absence of inputs from the somatosensory dorsal column nucleus occurring before the onset of auditory stimuli. The effects range from short-term suppression of spikes lasting a few milliseconds at the onset of the stimulus to long-term increases or decreases in spike rate that last throughout the duration of an acoustic stimulus (up to several hundred milliseconds). The long-term effect requires only a single electrical stimulus pulse to initiate and seems to be similar to persistent activity reported in other parts of the brain. Among the DCN inhibitory interneurons, only the cartwheel cells show a long-term rate decrease that could account for the rate increases (but not the decreases) of DCN principal cells. Thus even at the earliest stages of auditory processing, the represented information is dependent on nonauditory context, in this case somatosensory events.