Dataset Information

Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice.

ABSTRACT: Gap pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioral paradigm used for inferring the presence of tinnitus in animal models as well as humans. In contrast to pre-pulse inhibition (PPI), the neural circuitry controlling GPIAS is poorly understood. To increase our knowledge on GPIAS, a comparative study with PPI was performed in mice combining these behavioral tests and c-Fos activity mapping in brain areas involved in the inhibition of the acoustic startle reflex (ASR). Both pre-pulses and gaps efficiently inhibited the ASR and abolished the induction of c-Fos in the pontine reticular nucleus. Differential c-Fos activation was found between PPI and GPIAS in the forebrain whereby PPI activated the lateral globus pallidus and GPIAS activated the primary auditory cortex. Thus, different neural maps are regulating the inhibition of the startle response by pre-pulses or gaps. To further investigate this differential response to PPI and GPIAS, we pharmacologically disrupted PPI and GPIAS with D-amphetamine or Dizocilpine (MK-801) to target dopamine e?ux and to block NMDA receptors, respectively. Both D-amp and MK-801 efficiently decreased PPI and GPIAS. We administered Baclofen, an agonist GABA_B receptor, but failed to detect any robust rescue of the effects of D-amp and MK-801 suggesting that PPI and GPIAS are GABA_B-independent. These novel findings demonstrate that the inhibition of the ASR by pre-pulses or gaps is orchestrated by different neural pathways.

SUBMITTER: Moreno-Paublete R

PROVIDER: S-EPMC5302757 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice.

Moreno-Paublete Rocio R Canlon Barbara B Cederroth Christopher R CR

Frontiers in cellular neuroscience 20170207

Gap pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioral paradigm used for inferring the presence of tinnitus in animal models as well as humans. In contrast to pre-pulse inhibition (PPI), the neural circuitry controlling GPIAS is poorly understood. To increase our knowledge on GPIAS, a comparative study with PPI was performed in mice combining these behavioral tests and c-Fos activity mapping in brain areas involved in the inhibition of the acoustic startle reflex (ASR). Both pr ...[more]

PMID: 28239338

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Project description:The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR.

Project description:In vitro antibiotic susceptibility testing often fails to accurately predict in vivo drug efficacies, in part due to differences in the molecular composition between standardized bacteriologic media and physiological environments within the body. Here, we investigate the interrelationship between antibiotic susceptibility and medium composition in Escherichia coli K-12 MG1655 as contextualized through machine learning of transcriptomics data. Application of independent component analysis, a signal separation algorithm, shows that complex phenotypic changes induced by environmental conditions or antibiotic treatment are directly traced to the action of a few key transcriptional regulators, including RpoS, Fur, and Fnr. Integrating machine learning results with biochemical knowledge of transcription factor activation reveals medium-dependent shifts in respiration and iron availability that drive differential antibiotic susceptibility. By extension, the data generation and data analytics workflow used here can interrogate the regulatory state of a pathogen under any measured condition and can be applied to any strain or organism for which sufficient transcriptomics data are available. IMPORTANCE Antibiotic resistance is an imminent threat to global health. Patient treatment regimens are often selected based on results from standardized antibiotic susceptibility testing (AST) in the clinical microbiology lab, but these in vitro tests frequently misclassify drug effectiveness due to their poor resemblance to actual host conditions. Prior attempts to understand the combined effects of drugs and media on antibiotic efficacy have focused on physiological measurements but have not linked treatment outcomes to transcriptional responses on a systems level. Here, application of machine learning to transcriptomics data identified medium-dependent responses in key regulators of bacterial iron uptake and respiratory activity. The analytical workflow presented here is scalable to additional organisms and conditions and could be used to improve clinical AST by identifying the key regulatory factors dictating antibiotic susceptibility.

Dataset Information

Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice.

Publications

Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice.

Similar Datasets

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