Audition I Exam #3

Microelectrode Recording Technique

-Feature: thin tips with high impedance

-Advantages:

·Minimal damage it tissue and cells

·Better spatial selectivity

-High impedance —> larger spatial attenuation, therefore better spatial selectivity

-Thin tips —> fragile (therefore require surgery to open the access)

Gross (thick, macro) Electrodes Recording Technique

-Low impedance

-Larger tip diameter

-Poor spatial selectivity

-Tough

-Usually placed far away from the target

-Less invasive

Cochlear Microphonics (CM)

-A receptor potential that mimics the acoustic signal without latency. Cochlea works as a microphone

-Tasaki (1954): CM reverses polarity when electrode enters SM. This study shows that the CM is generated in organ of Corti, not auditory nerve

-CM is the reflection of AC (alternating current) receptor potential of HCs (in response to back-forth deflection of stereocilia)

-In response to the deflection of stereocilia, HC membrane potential changes from resting to depolarization, repolarization, hyperpolarization, repolarization repeatedly

AC and DC Signals

-AC: alternating current—alternating in direction

-DC: direct current—no change in direction

-Signal in cochlea:

·AC: (1) CM—AC membrane potential, (2) CAP—neuronal response

·DC: (1) EP, (2) SP, which is the DC membrane potential of HCs

CM generation and recording

-AC membrane potential and stereocilia deflecting:

·Laterally: depolarization

·Medially: hyperpolarization

·Back and forth, AC mimicking sound wave

-Recording can be done in:

·Intracellular recording

·Extracellular recording

·Outside cochlea

·Farther away from HCs, smaller the response

·**Unlike EP, CM is recordable outside the cochlea

CM input-output non-linearity

-The CM amplitude changes w/ stimulus level non-linearly; saturated and even rolled over at high sound levels

Characteristics of CM

-Waveform copies the input signal

·This feature is used in canceling CM by alternating average

-No latency

-Sensitive to cochlear status (i.e. damage)

-Non-linearity

Source of CM

-Hair cells, esp. OHCs are the source of CM. Evidence:

1. Extremely short latency (so not higher brain process)

2. Intracellular recording of OHC receptor potential represents CM waveform, largest amplitude

3. Eliminating OHCs almost totally eliminates CM

Compound Action Potential (CAP)

-N1 is from SGN dendrites with latency of ~1 ms, largely due to the synaptic delay (IHC-SGN synapse)

-N2 is from SGN axons with latency of 1.5-2 ms

-APs are generated at Ranvier's nodes

-CAP are the sum of APs from different ANFs and different nodes. Synchronization matters. This is why we see CAP only at onset and offset of sound

CAP and Synchrony

-CAP is the sum of APs from many ANFs

-CAP requires synchronized firing of ANFs in order to be recorded

-Synchronized firing occurs only at onset and offset where the stimulus shows transient

-ANFs in the high frequency region are better synchronized, due to higher speed of traveling wave and narrower region involved

-Synchrony is also better in response to transient signal (the signal with a fast change in time, such as slicks)

-Myelinated neurons are better synchronized

-Desynchrony is a disorder (i.e., auditory neuropathy)

Summation Potential (SP)

-A DC potential—does not change direction

-A receptor potential

·Without latency, like CM

·Generated from HCs (equally from IHCs and OHCs)

-Appears as a elevation of "baseline" in during CM

·Due to the potassium accumulation in HC during sound stimulation

·Stronger at high-frequency due to lack of time for removing K

-Is an item evaluated in ECochG, often together with CAP, sometimes useful in clinic

Types of Otoacoustic Emission

-Spontaneous: SOAE

-Evoked OAEs

·Transient evoked: TEOAE

·Stimulus following: OAE

·Distortion products: DPOAE

·Electrically evoked: EEOAE

-All involve new sound generated by cochlea (specifically by OHCs)

TEOAE

-Transient evoked Otoacoustic emission

-Exist in everyone with normal ears

-Latency depends on (1) signal frequency: higher frequency, shorter latency and (2) intensity: higher intensity, shorter latency

-Intensity function is nonlinear

-Spectrum of EOAE evoked is narrower than that of stimuli

DPOAE

-Distortion product Otoacoustic emissions

-External signal contains two primary tones: F1 and F2

-The sound recorded in the external ear canal can have frequency components other than F1 and F2: nF1 +/- mF2

-n and m are any integer numbers, but most likely, 2F1 - F2 (F1 < F2)

-Since DPOAE is a new sound (does not exist in the stimuli), this is more evidence showing the non-linearity nature of the cochlea

-A nonlinear system generates components that do not exist in the inputs signal

·We call these new components distortion products

-Not clear how DPOAE are generated

Clinical use of OAEs

-Evaluation of cochlear function

-Limited to OHCs: normal OAEs do not guarantee normal hearing

-Used as a screen tool

-Recent development in OAE suppression may extend the use of OAEs to evaluate brainstem function

OAE suppression and efferent function

-OHCs are innervated by cochlear efferent system (from superior olive complex)

-This efferent system can be activated by sound

-The evoked efferent system will suppress OHCs mobility—suppression of OAEs

-Tests of OAE suppression help to evaluate efferent functions as well as the integrity of low brainstem

-Clinical use is still limited due to poor S/N and big variation

Two types of afferent auditory neurons (SGNs)

-Type I (IHCs): bipolar cells

·Myelinated

·Thick fibers

-Type II (OHCs): pseudo-monopolar

·Unmyelinated

·Thinner

-Myelin sheath: lipid materials forming insulation—myelinization

·Functions: speed up signal conduction; reduce interference from other ANFs

Differences between type I and type II SGNs

-Type I:

·Myelination ensure insulation: no leaking (interference) for electrical signal from one fiber to another

·Ranvier node: AP jumping, save energy and increase speed

·Larger diameter: larger AP, higher AP conduction speed

·Response can be easily recorded

·85-95% of total SGNs

·Type I ANFs go radial direction: radial fibers

·Innervate IHCs, each IHC receives innervation from more than 10 type I SGN (10:1)—convergent innervation

-Type II:

·Thin (small diameter), no myelination

·Little is known about the functions of type II SGNs

·5-15% of total SGNs

·Innervate OHCs, each fiber innervates up to 16 OHCs (1:16)—divergent innervation

·Cross the tunnel of corti at the bottom, go to OHC region and then turned: outer spiral fibers

Ribbon Synapses

-Mainly seen in retina and inner ear

-This synapse is characterized as having ribbons in pre-synaptic regions

-Ribbons facilitate the release of neurotransmitter by holding the vesicles close to the active zone

-Play two roles in transmission: fasten the response and ensure long-lasting responses

-Glutamate is the only neurotransmitter likely involved in ribbon synapses

Efferent Innervations

-Originate in the superior olive complex (SOC) in brainstem

-The peripheral fibers pass through olive cochlea bundle (OCB)

-Divided in two groups: medial (MOCB) and lateral (LOCB)

-MOCB: mainly crossed (COCB), innervate OHC bodies, thick and myelinated

-LOCB: mainly uncrossed (UOCB), innervate IHCs (not on the IHC directly but on the afferent terminals below it), thin and unmyelinated, function not clear

-We know more about the function of MOCB than LOCB due to myelinated fibers creating larger APs (making them more likely to be recorded)

Information coding by neurons

-For important information encoding, AP waveform is not important

-How is the information encoded by APs?

·By single neuron, rate change in time sequence of firing

·By group of neurons, an array of firing (time and space—frequency)

Rutherford Frequency Theory

-Rutherford thought that the high frequency ANFs can fire at the frequency of sound (this is not true)

-Nerve fibers have refractory time of ~2 ms after each AP. Therefore the maximal firing rate is ~500 APs/second

Spontaneous and Driven APs

-Action potentials that are generated without an external signal (no stimulus) are called spontaneous APs

-The spontaneous APs are random in timing. External signal may be applied. However, if APs occur randomly, the neuron does not "hear" the sound. Or the sound level is below the threshold of the neuron

-Subjective tinnitus can be produced from spontaneous APs

Functional categorization of ANFs upon SRs

-There is a large difference across ANFs in the spontaneous rate (SR) of APs and the SR is used for grouping fibers

-ANFs are arbitrarily divided into 3 groups based upon SR from high, medium, to low

-The SR is closely (inversely) associated with threshold: lower the SR, higher the threshold

-Threshold/SR differences among ANFs—probably due to efferent innervation (LOC)

-There is a widespread distribution of the threshold for the fibers with low SR

SR is related to the synapse location to IHC by the ANF

-SGNs synapse around each IHC

-Fiber A: at modiolar side, likely to have low SR

-Fiber B: at pillar (OHC) side likely to have high SR

Differences Between Low SR and High SR ANFs

-Low SR ANFs:

·High thresholds, which are largely distributed across big SPL range

·Larger dynamic range in their rate-level functions

·More important for signal coding in noise (anti-masking)

·The synapse to low-SR ANFs are more sensitive to noise damage

-High SR ANFs are opposite in all above

What is the rate threshold?

-The sound level at which the firing rate is just above the spontaneous rate (when it is assumed the firing is due to stimulus)

Rate-level function of ANF

-RLF shows how spike rate changes with intensity (or SPL)

-If SPL changes cause spike rate changes, this is a dynamic response

-If SPL change does NOT cause spike rate change, this is NOT dynamic

-High SR units show narrower dynamic range

-Low SR units show a larger dynamic range

Dynamic range of high-SR ANFs

-Definition: the intensity range between the threshold and the level for the spike rate to plateau

-Typically 30-40 dB: if the threshold is 20 dB, the firing rate increases until 60 dB, then saturates

-The behaviour for high SR ANFs: low threshold, narrower dynamic range, and plateau at moderate sound level

Dynamic range of low-SR units

-Wider than high-SR units

-Not really saturated at high sound level

-Therefore more capable of coding sound against strong background noise where the high-SR fibers are saturated

Frequency Coding by AN

-Frequency info is coded mainly by two mechanisms:

·Place code: ANFs innervating IHCs at different places along cochlea show different frequency feature

·Temporal coding: ANFs change their firing pattern based upon temporal information that is related with frequency

Threshold tuning curves

-Threshold tuning curves: showing the lowest sound level (y axis) that can drive the ANF to fire

Characteristic Frequency (CF)

-The frequency that corresponds to the lowest threshold of the ANF

-Closer to the apex, CFs are low

-Closer to the base, CFs are high

The impact of OHCs on RLF

-The different RLFs across CF are due to the OHC active mechanism, which is level and frequency dependent—it acts at narrow frequency region and at low-moderate sound level

-OHCs provide larger gain for soft sound and no amplification at high sound level, causing the plateau at high sound levels

Temporal firing pattern

-Often shown as post (or peri) stimulus histogram (PSTH)

-PSTH count the number of spikes in each time bin after the onset stimulus

PSTH

-The PSTH shows a response that goes through 5 stages:

·Onset peak, fast then slow adaptation, offset depression, and recovery

Phase locking

-ANFs more likely to fire at depolarization phase: phase/time locking

-Phase locking is stronger at low frequencies

Bilateral projection to auditory cortex

-SOC: the first bilateral center (the cochlear nucleus (CN) only receives unilateral input))

-Above the SOC, every nucleus receives bilateral projections from lower level

-Contralaterally dominated: stronger innervation from/to the opposite side above CN

-Asymmetric between both hemispheres:

·Left: language

·Right: music, spatial, logic

Hierarchical organization of the CAS

-Higher level nuclei usually have:

·More complicated structures

·Larger number of neurons

·Multiple types of neurons (morphological and functional diversity)

·More sophisticated signal processes (involving the interaction between excitation and inhibition, neural circuits)

·Control to lower levels through efferent system

·Interaction with other systems

Signal processing at different levels

-Lower-level neurons do simple processing

-Unprocessed signal features (if important) must be delivered to the higher level

-Integration across neurons

Topographic Organization—Place Coding

-Tonotopic map in auditory system—exists in cochlea, and inherited/enhanced in CAS from CN to AC

Relay and Interneurons

-Relay neurons (principle neurons):

·Receive input from and send output to outside nuclei

·Input from lower level, output to higher level

·Relay by synapse

·Some nuclei may not be relayed and can bypass to the next nucleus. For example, projection can go from CN to IC, by-passing SOC and LL (lateral lemniscus) nuclei

·In other nuclei, the projection must be relayed. One example is CNs

-Interneurons:

·Make synapses inside the nucleus (locally)

·Circuits around relay neurons

Multiple ascending pathways due to relay and bypass

-Nuclei where relay is a must: CN, IC, MGB

-Shortest pathway: CN directly to IC

-Longest pathway: CN-MNTB-LSO-NLL-IC

**MNTB: medial nucleus of the trapezoid body

**NLL: nuclei of the lateral lemniscus

**LSO: lateral superior olivary nucleus

Cochlear Nucleus (CN): 3 Major Divisions

-Dorsal CN (DCN)

-Anterior ventral CN (AVCN)

-Posterior ventral CN (PVCN)

-VCN is much larger than DCN

-High frequencies in dorsal location

-Each SGN enters and goes to three different spots (DCN, AVCN, PVCN)

-Both the VCN and DCN are tonotopically organized: CF changes with electrode insertion

Multiple cellular types and segragation

-Spherical/globular bushy cells in AVCN and PVCN

·Spherical bushy cells in AVCN-A

·Globular bushy cells in AVCN-P

-Octopus cells in PVCN-P

Bushy cells: spherical and globular types

-Endbulbs of Held: special synapse for AVCN neurons with SGNs

-Ensure good timing which is important for sound localization

-Binaural convergent projection from AVCN to SOC for sound localization

Octopus Cells

-Large dendrites

-Strong response to transient—temporal processing

-Sensitive to frequency moderation direction

·Neuron will be excited if the frequency change results in an excitation sequence from 6 to 1

Inhibition

-It is a central mechanism

-No inhibition in cochlea

-Contribute to every aspect of signal processing in CAS

-One of the reasons for functional diversity

-Inhibition requires inhibitory neurons and neurotransmitters

-Interneurons can send inhibitory neurotransmitters to principle neurons (relay neurons)

Inhibition seen in PSTH

-Inhibition is clearly seen in off and inhibitory types of PSTH

Response area graphs showing inhibition

-Type I: no inhibition, seen in response of ANFs

-Type II and III: excitatory area + inhibitory side band

-Type III, IV, and V neurons have spontaneous APs

-Type II neurons have no spontaneous APs

Inhibition in rate-level function

-Monotonic pattern: not as much inhibition at higher sound levels

-Non-monotonic pattern: suggests more inhibition at high sound levels (due to big drop off of firing rate at higher sound levels)

Inhibitory neurotransmitters

-Glycine and GABA: two major inhibitory neurotransmitters

-How to verify inhibition?

·Apply blocker to inhibitory neurotransmitter

·Compare neural activity with and without the blocker

·The difference is resulted from inhibition

Nuclei in superior olive complex (SOC)

-Three major nuclei:

·LSO: lateral superior olive

·MSO: medial superior olive

·MNTB: medial nuclei of trapezoid body

SOC is first station for sound source localization

-SOC is the first station in which binaural inputs merge. Therefore, it is the place for using binaural cues in sound localization

-Binaural cues are important for sound localization in horizontal plane

-Binaural cues are differences of sound between ears

·Interaural time difference (ITD)

·Interaural level/intensity difference (ILD or IID)

Binaural cues and signal frequency

-For low frequency sounds, ITD is more important, ILD/IID is small because less shadow effect

-For high frequency sounds, ILD/IID is more important, especially for small animals: the small head makes the ITD too small between their two ears

-For larger animals, ILD/IID is also important

MSO

-Larger than LSO in humans and other large animals

-Binaural processing mainly the low frequency cues in the form of ITD

-ITD is produced by acoustic delay, cues for sound localization

-In small animals, MSO is less developed

-AVCN projects directly to MSOs of both sides (bilateral)

LSO

-LSO is larger than MSO in smaller animals

-Mainly process binaural level difference of high-frequency sound

-Sensitive to IID

-Direct input to LSO from one ear: only ipsilateral

Medial nucleus of the trapezoid body (MNTB)

-AVCN input to MNTB (contralaterally) via synapse called Calyx of Held

-Neurons in both MSO and MNTB are involved in ITD process for sound localization

Central IC (ICC)

-The only part of IC showing a clear tonotopic map

Medial geniculate body (MGB)

-Three major division: ventral, dorsal and medial

-Ventral division shows clear tonotopic map

-Functions of dorsal and medial division are not clear

Primary Auditory Cortex

-Primary auditory cortex is Brodmann area 41

-Location: transverse gyri of Heschl

-Also called koniocortex

Secondary Auditory Cortex

-Brodmann area 42

-Also called parakoniocortex

-It surrounds area 41

-Katz hypothesizes that the surface of area 41 and 42 cannot be clearly separated because the apical dendrites are surrounded by the connection from area 42

Associative AC: Planum Temporale and Superior Temporal Gyrus

-Planum temporale: Brodmann area 22

·Posterior part of the superior temporal gyrus

·Called Wernicke's area in the dominant side (90% have left side dominance)

Language-Related Cortices and Their Connections

-Arcuate Fasciculus: connects area 22 (Planum temporale/wernicke's area) and Broca's area

-Inferior parietal lobule: integration center between auditory and visual inputs

-Broca's area: motor language area—often located in the left hemisphere of humans