Antonio G. Paolini

Temporal processing from the auditory nerve to the medial nucleus of the trapezoid body in the rat

This investigation examines temporal processing through successive sites in the rat auditory pathway: auditory nerve (AN), anteroventral cochlear nucleus (AVCN) and the medial nucleus of the trapezoid body (MNTB). The degree of phase-locking, measured as vector strength, varied with intensity relative to the cells threshold, and saturated at a value that depended upon stimulus frequency. A typical pattern showed decline in the saturated vector strength from approximately 0.8 at 400 Hz to about 0.3 at 2000 Hz, with similar profiles in units with a range of characteristic frequencies (480-32,000 Hz). A new expression for temporal dispersion indicates that this variation corresponds to a limiting degree of temporal imprecision, which is relatively consistent between different cells. From AN to AVCN, an increase in vector strength was seen for frequencies below 1000 Hz. At higher frequencies, a decrease in vector strength was observed. From AVCN to MNTB a tendency for temporal coding to be improved below 800 Hz and degraded further above 1500 Hz was seen. This change in temporal processing ability could be attributed to units classified as primary-like with notch (PL(N)). PL(N) MNTB units showed a similar vector strength distribution to PL(N) AVCN units. Our results suggest that AVCN PL(N) units, representing globular bushy cells, are specialised for enhancing the temporal code at low frequencies and relaying this information to principal cells of the MNTB.

Topographic Organization in the Auditory Brainstem of Juvenile Mice is Disrupted in Congenital Deafness

There is an orderly topographic arrangement of neurones within auditory brainstem nuclei based on sound frequency. Previous immunolabelling studies in the medial nucleus of the trapezoid body (MNTB) have suggested that there may be gradients of voltage‐gated currents underlying this tonotopic arrangement. Here, our electrophysiological and immunolabelling results demonstrate that underlying the tonotopic organization of the MNTB is a combination of medio‐lateral gradients of low‐and high‐threshold potassium currents and hyperpolarization‐activated cation currents. Our results also show that the intrinsic membrane properties of MNTB neurones produce a topographic gradient of time delays, which may be relevant to sound localization, following previous demonstrations of the importance of the timing of inhibitory input from the MNTB to the medial superior olive (MSO). Most importantly, we demonstrate that, in the MNTB of congenitally deaf mice, which exhibit no spontaneous auditory nerve activity, the normal tonotopic gradients of neuronal properties are absent. Our results suggest an underlying mechanism for the observed topographic gradient of neuronal firing properties in the MNTB, show that an intrinsic neuronal mechanism is responsible for generating a topographic gradient of time‐delays, and provide direct evidence that these gradients rely on spontaneous auditory nerve activity during development.

Long-term sensorineural hearing loss induces functional changes in the rat auditory nerve.

Loss of cochlear hair cells in the rat initiates degenerative change within the primary auditory neurons (ANs) of the cochlea. These degenerative changes include loss of peripheral processes, demyelination and ultimately cell death. This pathology will affect the biophysical processes involved in action potential generation and propagation to an electrical stimulus via a cochlear implant. We measured the response properties of ANs, with particular reference to their refractory behaviour, in normal, short‐ (9 weeks) and long‐term (> 52 weeks) deafened rats. AN loss was moderate in the short‐term and severe in the long‐term deafened animals. AN activity was elicited using a brief electrical stimulus delivered via a bipolar electrode array implanted into the cochlea. The general response properties of ANs recorded from deafened cochleae were similar to those observed in normal cochleae, i.e. a monotonic increase in the probability of firing and a decrease in response latency and temporal jitter with increasing stimulus intensity. However, the absolute refractory period was significantly prolonged in animals deaf for > 12 months (P = 0.0026). Deafened animals also exhibited a highly significant increase in threshold compared with normal controls (P < 0.001). These functional changes have implications for recipients of cochlear implants and potential therapies directed toward halting or reversing AN pathology.

Effects of adult-onset calorie restriction on anxiety-like behavior in rats.

Calorie restriction (CR) has consistently been shown to increase lifespan and ameliorate disease outcomes. Its effects on behavior are less clear, although anxiolytic-like effects have been observed. Rats were subjected to 1 of 4 dietary regimens: control, CR25%, CR50% and, an acute episode of CR and tested in 3 tests of anxiety: the open field test, the elevated plus maze, and the modified open field test. In the open field test, the CR25% and CR50% groups made more central zone entries than the control and Acute groups, which was primarily due to differences in the initial 5 min of the test. Moreover, both CR groups engaged in greater exploration of the central zone than the control group in the initial 5 min of the test. The Acute group also exhibited significantly longer latencies to leave the central zone at test onset than the control and CR50% group. In the elevated plus maze, the Acute group also displayed longer latencies to open arm entry as compared to the control and CR50% group and showed a lower ratio of open to total arm entries compared to all other groups. There were no effects of CR on any variable of the modified open field test. Possible neurochemical mechanisms underlying the anxiolytic-like effect of CR are discussed.

Conducting polymer coated neural recording electrodes

OBJECTIVE Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. APPROACH Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. MAIN RESULTS A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. SIGNIFICANCE A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during acute implantation, inferring good biostability. Electrode impedance at 1 kHz was correlated with background noise and inversely correlated with signal to noise ratio and spike count, regardless of coating. These results collectively confirm a potential for improvement of neural electrode systems by coating with conducting polymers.

Audiovisual integration in noise by children and adults

The aim of this study was to investigate the development of multisensory facilitation in primary school-age children under conditions of auditory noise. Motor reaction times and accuracy were recorded from 8-year-olds, 10-year-olds, and adults during auditory, visual, and audiovisual detection tasks. Auditory signal-to-noise ratios (SNRs) of 30-, 22-, 12-, and 9-dB across the different age groups were compared. Multisensory facilitation was greater in adults than in children, although performance for all age groups was affected by the presence of background noise. It is posited that changes in multisensory facilitation with increased auditory noise may be due to changes in attention bias.

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Calorie restriction (CR) has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25% (CR25%) or restricted 50% (CR50%) in food intake for 28 days and injected with 50 μg/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50% for 28 days, and hypothalamic mRNA expression of inhibitory factor κB-α (IκB-α), cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50% mice did not develop fevers, whereas the CR25% mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25% and CR50% mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50% animals preinjection compared with controls. The CR50% mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and IκB-α expression in CR50% animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways.

Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

Effect of Age and Cognition on Childhood Speech in Noise Perception Abilities

This research on children’s speech in noise and cognitive abilities aimed to determine the age-related trends in speech in noise perception abilities and the relationship between speech in noise perception and cognitive abilities. Monosyllabic distinguishable (consonant-vowel-consonant) words was the most recognisable word category, followed by monosyllabic confusable words (consonant-vowel-consonant), disyllabic non-words (/aCa/) and monosyllabic syllables (/Ca/), demonstrating that phoneme distinctiveness and a reduction in word confusability contribute to their recognition. Older children outperformed younger children on all speech in noise tasks, indicating that there are age-related trends in speech in noise abilities. Children with higher cognitive abilities did not outperform children with lower cognitive abilities on speech in noise tasks, indicating that the ability to hear speech in noise may be an intrinsic feature of the auditory system that matures with age.

Maturation of auditory brainstem projections and calyces in the congenitally deaf (dn/dn) mouse.

The deaf dn/dn mouse is a valuable model of human congenital deafness. In this study we used the lipophylic dye DiA to trace auditory nerve and cochlear nucleus projections in the dn/dn mouse. In both normal and deaf mice, the ipsilateral projections from the anteroventral cochlear nucleus (AVCN) to the lateral superior olive (LSO), and the contralateral projections from the AVCN to the medial nucleus of the trapezoid body (MNTB) were intact. With age, there was a noted increase in the fenestration of the endbulb and calyx of Held, and this morphological maturation was also observed in the deaf mice, although there was a significant difference in total endbulb volume at P20 between normal and deaf mice. However, total calyceal volume was not significantly different between normal and deaf mice. There was electrophysiological evidence of in vivo spontaneous ventral cochlear nucleus activity in normal and deaf animals, indicating that this activity may be responsible for the appropriate connectivity in the deaf mice. Our results indicate that congenital deafness caused by the dn/dn mutation does not result in aberrant projections between the AVCN and the ipsilateral MNTB and contralateral LSO but can cause abnormalities in endbulb size. J. Comp. Neurol. 506:442–451, 2008.