Viva questions Flashcards
(28 cards)
Contribution of other auditory pathway structures like the MGB
• Blackwell et al. (2020) demonstrated that the medial geniculate body (MGB) relays information from the inferior colliculus (IC) to the auditory cortex (AC) in the ascending auditory pathway.
• The ventral MGB projects tonotopically to A1, while the dorsal MGB carries multimodal sensory information and the medial MGB connects to limbic systems such as the hippocampus.
• Future experiments could involve silencing the MGB during corticocollicular activation to reveal its role in feedback modulation of IC neurons.
Role of other cortical layers in corticocollicular projections
• Layer 5 neurons provide the primary corticocollicular output, projecting strongly to the IC.
• Layer 6 neurons primarily project to the thalamus (MGB), modulating thalamocortical relay.
• Layers 2/3 mainly facilitate local intracortical signaling without direct subcortical outputs.
• Layer 4 acts as the main thalamorecipient layer, feeding information into upper cortical layers.
• Layer 1 contains dendritic fields for integration but does not directly project to subcortical targets.
Specific higher-order auditory areas and their role in prediction
• Higher-order areas like A2 (secondary auditory cortex) integrate complex auditory patterns and generate predictive signals that influence subcortical structures.
• The posterior ectosylvian gyrus (PEG) integrates auditory and multimodal information, while the ventral auditory field (VAF) supports memory-based prediction error computation.
• Lesicko et al. (2022) showed that such higher-order areas actively contribute to hierarchical predictive coding within the auditory system.
Conditions that could study corticocollicular plasticity
• Corticocollicular plasticity can be studied using monaural deprivation (ear occlusion) as shown by Bajo et al. (2010).
• Noise trauma experiments induce adaptive changes within auditory pathways.
• Active listening tasks compared to passive (Price et al.) reveal enhanced brainstem responses.
• Oddball paradigms can assess prediction error mechanisms by presenting unexpected auditory stimuli.
Differences between human and ferret corticocollicular systems
- In ferrets, corticocollicular projections are predominantly ipsilateral from A1 to dorsal and lateral regions of IC.
- In humans, imaging studies suggest active cortical feedback to subcortical stations during attention-demanding tasks (Price et al.).
- Ferrets have a hearing range of approximately 40–30 kHz, while humans hear from about 20 Hz to 20 kHz.
- These ranges are calculated using audiograms and electrophysiological measurements such as ABR and FFR recordings.
What happens to sound after the IC?
• After processing in the IC, sound information projects to the medial geniculate body (MGB), and then to the auditory cortex.
• Early stages involve cochlear nuclei, superior olivary complex (SOC), and lateral lemniscus, with bilateral integration occurring at multiple levels including IC and SOC.
What is the cocktail party effect?
- The cocktail party effect describes the ability to selectively attend to one speaker among multiple competing auditory stimuli.
- This effect relies on grouping cues such as pitch, location, and timing.
- Price et al. used phase transfer entropy to demonstrate enhanced auditory encoding during active listening compared to passive conditions.
ILD sensitivity and how ILD is calculated
- ILD sensitivity is crucial for localizing high-frequency sounds and involves comparing sound intensity differences between ears.
- Brainstem structures such as the lateral superior olive (LSO) process ILD cues to support auditory spatial perception.
How can we clarify monosynaptic corticocollicular connectivity?
- Pair ChR2 with pharmacology, blocking voltage-gated sodium channels with TTX or Potassium channels with 4AP Aps and thereby polysnaptic inputs can be prevented
What is the contribution of inhibitory circuits?
- Inhibitory circuits contribute to corticocollicular signaling as shown by Blackwell et al. (2020).
- Suppressing somatostatin (SST) interneurons significantly altered IC spontaneous firing, whereas parvalbumin (PV) interneurons had less influence.
- Cholinergic inputs from the nucleus basalis also modulate cortical output to the IC.
Laminar differences in corticocollicular neuron inputs
- Layer 5 integrates signals from both excitatory and inhibitory circuits, facilitating corticocollicular projections.
- Layer 6 primarily processes local cortical activity and projects mostly to thalamic regions rather than directly to IC.
Viral vector and optogenetic design
- RetroAAV-Cre was injected into the IC to label corticocollicular neurons retrogradely.
- AAV-FLEX-ChR2-mCherry was injected into the auditory cortex, ensuring expression only in Cre-positive corticocollicular neurons (Blackwell et al., 2020).
Cre controls and optogenetics off-target effects
- Cre controls included no-Cre virus injections and light-only controls to exclude nonspecific effects.
- Off-target effects such as heating or unintended axonal activation were minimized through rigorous experimental controls.
Neuropixels probe and motion correction
- The Neuropixel 3a probe features a single shank with 384 titanium nitride-coated electrodes.
- On-chip analog and digital circuitry allow high-density, stable recordings with minimal signal loss.
PSTH construction and limitations
- Peristimulus time histograms (PSTHs) were generated by aligning spike trains to stimulus onset using fixed pre- and post-stimulus bins.
- While response type classification was considered, overlap among neuron types limited its inclusion in final analyses.
Surgical procedures for virus delivery and reagents used
- Surgical procedures included the use of medetomidine, ketamine, and isoflurane anesthesia.
- Euthanal (pentobarbital) was used for humane euthanasia.
- Paraformaldehyde was used for brain fixation.
- Buprenorphine and meloxicam provided perioperative analgesia, and antibiotics were used to prevent infection.
Wilcoxon signed-rank test — purpose and justification
- The Wilcoxon signed-rank test is a non-parametric paired test used when the assumption of normality is violated.
- It tests whether the median difference between paired observations equals zero.
Shapiro-Wilk test for normality
- The Shapiro-Wilk test checks whether a dataset significantly deviates from a normal distribution.
- A non-significant result (p>0.05) implies normality, allowing use of parametric tests.
One-way ANOVA and Tukey post hoc
- One-way ANOVA tests for overall differences across multiple group means.
- Tukey’s post hoc test identifies specific group differences while controlling for multiple comparisons.
Two-way ANOVA
- Two-way ANOVA analyzes the main effects and interaction between two independent variables.
- It allows understanding of how different experimental factors influence a dependent variable both independently and jointly.
Why use non-parametric tests sometimes even with large samples?
- Non-parametric tests are preferred when distributions are highly skewed, heavy-tailed, or bimodal even at large sample sizes.
- They offer robust results at the cost of reduced statistical power compared to parametric alternatives.
Have you looked at different cortical layers?
- The optogenetic protocol illuminated all cortical layers, but activation was specific to layer V and deep layer VI neurons projecting to the IC.
- Confocal microscopy confirmed the cortical distribution of viral expression across layers.
What is the structure of a neuropixel 3a recording probe?
- The Neuropixel 3a probe consists of a single shank with 384 biocompatible titanium nitride electrodes ranging from 25–150 μm².
- The probe integrates on-chip analog and digital processing for signal acquisition.
How does the Neuropixel software work?
- Neuropixel software corrects for relative probe motion by tracking unit displacement across time.
- Post-hoc alignment ensures longitudinal recording stability even in mobile preparations.
