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Fischer Brown Norway (FBN) rats (n = 233) were unilaterally exposed to 12 different combinations of noise intensity, duration, and spectrum, while 46 rats served as sham-exposed controls. Rats were behaviorally tested for tinnitus and hyperacusis using gap-induced inhibition of the acoustic startle reflex (Gap) and prepulse inhibition (PPI) using 60-dB SPL before noise-exposure and at regular intervals for 12 mo. 12-mo after noise exposure the middle-aged rats were then tested again for tinnitus and hyperacusis before collecting Auditory Brainstem Response (ABR) thresholds. Collapsing across all noise exposure conditions a significant tinnitus-like deficit in responding to silent gaps was observed, with the most likely tinnitus pitch around 16 kHz. Rates of tinnitus 12-mo after noise exposure were greatest in groups receiving the four least intense noise doses (110-dB for 30, 60 and 120 min, and 116-dB for 30 min), while some of the greatest rates of hyperacusis occurred in groups receiving more intense or longer exposures. The results suggest that rates for developing tinnitus in animal models may not be easily predicted based upon noise exposure dose, but that low-to-moderate noise exposures may result in the greatest likelihood for producing tinnitus. [ABSTRACT FROM AUTHOR]

Abstract: Presbycusis can be considered a slow age-related peripheral and central deterioration of auditory function which manifests itself as deficits in speech comprehension, especially in noisy environments. The present study examined neural correlates of a simple broadband noise stimulus in primary auditory cortex (A1) of young and aged Fischer–Brown Norway (FBN) rats. Age-related changes in unit responses to broadband noise bursts and spontaneous activity were simultaneously recorded across A1 layers using a single shank, 16-channel electrode. Noise bursts were presented contralateral to the left A1 at 80dB SPL. Aged A1 units displayed increased spontaneous (29%), peak (24%), and steady state response rates (38%) than did young A1 units. This was true across all A1 layers, although age-related differences were significantly greater for layers I–III (43% vs 18%) than lower layers. There was a significant age-related difference in the depth and duration of post-onset suppression between young and aged upper layer A1 units. The present functional differences across layers were consistent with studies showing greatest losses of gamma-aminobutyric acid (GABA) markers in superficial layers of A1 and with anatomic studies showing highest levels of inhibitory neurons located in superficial cortical layers. The present findings were also consistent with aging studies suggesting loss of functional inhibition in other cortical sensory systems. [Copyright &y& Elsevier]

Abstract: Aims: The type 2 muscarinic receptor (M2R) differs from the other G-protein-coupled muscarinic receptor (type 4, or M4R) in tissue distribution and physiologic effects. We studied the impact of these receptors on sleep and arousal by using M2R and M4R knock-out (KO) mice. Main methods: M2R and M4R KO and genetically intact mice were compared in terms of normal patterns of sleep, responses to sleep loss, infectious challenge and acoustic startle, and acoustic prepulse inhibition of startle (PPI). Key findings: Under basal conditions, M2R and M4R KO mice do not differ from the background strain or each other in the amount or diurnal pattern of sleep, locomotor activity, and body temperature. After enforced sleep loss, M2R KO mice, in contrast to the other two strains, show no rebound in slow-wave sleep (SWS) time, although their SWS is consolidated, and they show a greater rebound in time spent in REMS (rapid-eye-movement sleep) and REMS consolidation. During influenza infection, M2R KO mice, as compared with the other strains, show marked hypothermia and a less robust increase in SWS. During Candida albicans infection, M2R KO mice show a greater increase in SWS and a greater inflammatory response than do the other strains. M2R KO mice also show greater acoustic startle amplitude than does the background strain, although PPI was not different across the 3 strains over a range of stimulus intensities. Significance: Taken together, these findings support different roles for M2R and M4R in the modulation of sleep and arousal during homeostatic challenge. [Copyright &y& Elsevier]

Abstract: Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern. [Copyright &y& Elsevier]

Reports that the LIM protein FHL3 binds basic Kruppel-like factor/Kruppel-like factor 3 and its co-processor C-terminal-binding protein 2. Evidence that CtBP2 interacts with FHL3; Demonstration that the proteins co-elute in gel filtration experiments; Importance of LIM proteins like FHL3 in assembling specific repression or activation complexes.

Focuses on a study which showed that GC-type elements play important roles in the control of tissue-specific genes as well as ubiquitously expressed genes and that the transcription factor SP1 is a member of an extensive family of factors. Features of the SP1 family; Differences within the family; Discussion on the results of the study.

An abstract of the article "Behavioral measures of tinnitus in laboratory animals," by Jeremy G. Turner is presented.

Abstract: Diseases of the endocrine system are common and many require surgical management. Equipped with an understanding of a few physiological principles, the complexity of the endocrine system becomes much less daunting. This contribution emphasizes these physiological principles and illustrates their clinical relevance. [Copyright &y& Elsevier]

Abstract: Neurophysiological studies of salicylate-induced tinnitus have generally been carried out under anesthesia, a condition that abolishes the perception of tinnitus and depresses neural activity. To overcome these limitations, measurement of salicylate induced tinnitus were obtained from rats using schedule induced polydipsia avoidance conditioning (SIPAC) and gap pre-pulse inhibition of acoustic startle (GPIAS). Both behavioral measures indicated that tinnitus was present after treatment with 150 and 250mg/kg of salicylate; measurements with GPIAS indicated that the pitch of the tinnitus was near 16kHz. Chronically implanted microwire electrode arrays were used to monitor the local field potentials and spontaneous discharge rate from multiunit clusters in the auditory cortex of awake rats before and after treatment with 150mg/kg of salicylate. The amplitude of the local field potential elicited with 60dB SPL tone bursts increased significantly 2h after salicylate treatment particularly at 16–20kHz; frequencies associated with the tinnitus pitch. Field potential amplitudes had largely recovered 1–2 days post-salicylate when behavioral results showed that tinnitus was absent. The mean spontaneous spike recorded from the same multiunit cluster pre- and post-salicylate decreased from 22spikes/s before treatment to 14spikes/s 2h post-salicylate and recovered 1 day post-treatment. These preliminary physiology data suggest that salicylate induced tinnitus is associated with sound evoked hyperactivity in auditory cortex and spontaneous hypoactivity. [Copyright &y& Elsevier]

Abstract: The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show neurotransmitter and functional age-related changes suggestive of a downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory circuits implicated in these changes include vertical and D-multipolar cells. Cartwheel cells comprise a large additional population of DCN inhibitory neurons. Cartwheel cells receive excitatory inputs from granule cell parallel fibers and provide a source of glycinergic inhibitory input onto apical dendrites of DCN fusiform cells. The present study compared the response properties from young and aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit recordings from aged cartwheel cells revealed significantly higher thresholds, increased spontaneous activity and significantly altered rate-level functions characterized by hyperexcitability at higher intensities. Aged cartwheel cells showed a significant reduction in off-set suppression. Collectively, these findings suggest a loss of tonic and perhaps response inhibition onto aged DCN cartwheel neurons. These changes likely reflect a compensatory downregulation of synaptic inhibition in response to a loss of excitatory drive from auditory and non-auditory excitatory inputs via granule cells. The impact of increased excitability of cartwheel cells on DCN output neurons is likely to be complex, influenced by loss of glycinergic release and/or subunit receptor changes which would only partially off-set age-related loss of inhibition onto the somata and basal dendrites of fusiform cells. [Copyright &y& Elsevier]