Physiology II - Auditory Nerve and Efferent notes PDF

CMSD5280 Audition II Physiology #2: Auditory Nerve and Efferent Dr. Olivier Valentin, Ph.D. OUTLINE Fundamental biology concepts Outer and inner hair cells The afferent (=ascending) pathway Coding Mechanisms in the Auditory Pathway The efferent (=descending) pathway Fundamenta...

CMSD5280 Audition II Physiology #2: Auditory Nerve and Efferent Dr. Olivier Valentin, Ph.D. OUTLINE Fundamental biology concepts Outer and inner hair cells The afferent (=ascending) pathway Coding Mechanisms in the Auditory Pathway The efferent (=descending) pathway Fundamental biology concepts 1- What is a neuron?  Neurons are the fundamental units of the nervous system, specialized for receiving, processing, and transmitting information. At the top of the neuron are the dendrites, which are branch-like extensions that receive incoming signals from other neurons or sensory inputs. These signals are then passed to the cell body, or soma, which contains the nucleus—the control center of the neuron that regulates its functions and houses genetic material. Extending from the cell body is the axon, a long, slender projection that transmits electrical impulses away from the cell body. At the end of the axon are the axon terminals, which establish connections with other neurons, muscles, or glands through structures called synapses. These terminals release chemical messengers, or neurotransmitters, that allow communication between cells. The arrow on the left illustrates the general direction of information flow, starting from the input at the dendrites, passing through the cell body, and traveling down the axon to the output at the axon terminals. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed  Some neurons, like the one shown here, are myelinated, meaning their axons are wrapped in a fatty layer called the myelin sheath, produced by specialized cells such as Schwann cells. The myelin sheath is segmented, with gaps called the nodes of Ranvier. This structure allows electrical impulses to travel much faster along the axon by jumping from node to node in a process called saltatory conduction (this will be explored later). Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar  Neurons come in a variety of shapes and structures, each adapted to specific roles within the nervous system. Unipolar Neurons have a single process extending from the cell body that branches into a peripheral process and a central process. Unipolar neurons only occurTrusted Source in invertebrates, such as flies, and are not present in humans. In invertebrates, unipolar neurons play a role in the glands and muscles. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar  Bipolar neurons have two distinct processes: one dendrite and one axon, extending from opposite sides of the cell body. They are rare and mainly found in specialized sensory organs, such as the retina of the eye or the olfactory system. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar  Multipolar neurons are the most common type of neuron in the body. They have one axon and multiple dendrites, allowing them to integrate information from many sources. Multipolar neurons are primarily found in the brain and spinal cord, playing a key role in motor control and integration. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar  Unlike other neurons, anaxonic neurons lack a distinct axon. Instead, they have only dendrites and are involved in local signal processing in the brain, particularly in regions like the retina. Their exact functions are still not fully understood. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar  The pseudounipolar neurons are a variant of unipolar neurons. They have a single process that splits into two branches: one acting as a dendrite to receive sensory input and the other as an axon to transmit signals. They are commonly found in human sensory ganglia, such as those of the spinal cord. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons  Motor neurons are responsible for transmitting signals from the central nervous system to muscles or glands, enabling movement or secretion. On the upper left image, we can see a multipolar motor neuron, which is characterized by multiple dendrites and a single axon. The motor neuron connects directly to a muscle fiber, allowing it to transmit electrical impulses that stimulate muscle contraction. On the bottom right corner, we have an immunofluorescence micrograph of Drosophila flight muscles, where motor neurons are stained in red, the muscles in blue, and the neuromuscular junctions are highlighted in green and yellow. As you can see, the connections between motor neurons and muscle fibers are very intricate, underscoring the complexity of how the nervous system controls movement at the cellular level. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons  Interneurons act as bridges or connectors within the central nervous system. They transmit signals between other neurons, and they are crucial for processing and integrating information. In the diagram here, we have a multipolar interneuron, which has many dendrites and one axon. Notice that its axon terminals make connections with the dendrites of two other multipolar neurons. This reflects the role of interneurons in forming circuits within the brain and spinal cord. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons  Sensory neurons are specialized to carry sensory information from sensory receptors to the central nervous system, where it is processed and interpreted. In the auditory system, sensory neurons are typically pseudounipolar, meaning they have a single axon that branches into two parts, one extending to the sensory receptor and the other to the brain. However, other sensory systems may use different types of neurons. For example, the sensory neurons of the retina are bipolar neurons, with two extensions—one for receiving input from photoreceptors and the other for transmitting the signal to the brain. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse  When the hair bundle is deflected toward the tallest stereocilium, cation-selective channels near the tips of the stereocilia open, allowing K⁺ ions from the endolymph to flow into the hair cell down their electrochemical gradient. The resulting depolarization of the hair cell opens voltage-gated Ca²⁺ channels in the soma, which triggers synaptic vesicles to fuse with the terminal membrane and release neurotransmitters into the synaptic cleft. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission  The neurotransmitters bind to ionotropic receptors on the postsynaptic membrane, causing these channels to open and allowing ions to flow into the postsynaptic neuron. If the resulting depolarization reaches the threshold potential (~-55 mV), voltage- gated Na⁺ channels in the postsynaptic membrane open, initiating an action potential. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse t (ms)  At rest, the postsynaptic neuron has a negative membrane potential (~-70 mV), maintained by the Na⁺/K⁺ pump and selective ion permeability. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse t (ms)  When neurotransmitters stimulate the postsynaptic neuron and the membrane potential reaches the threshold, Na⁺ channels open, and sodium ions rush into the cell, making the interior more positive (depolarization phase). This depolarization is self-amplifying, as more Na⁺ channels open in response. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse t (ms)  At the peak of the action potential (~+30 mV), Na⁺ channels inactivate, and voltage-gated K⁺ channels open, allowing K⁺ to flow out of the cell. This repolarization restores the membrane potential to a negative value. [click] A brief hyperpolarization may occur before the Na⁺/K⁺ pump restores the resting potential. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse  To sum up, when the neuron is stimulated, it generates an action potential, allowing Na+ to enter the cell, depolarizing the membrane and triggering an action potential in the adjacent region. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse  As the original site of the membrane restores its negative potential through the opening of K+ channels, the adjacent membrane undergoes depolarization due to Na+ entering at that location. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse  This sequential cycle of depolarization and repolarization enables the action potential to propagate along the membrane. Fundamental biology concepts 1- What is a neuron? 2- Myelination and conduction speed 3- Unipolar vs bipolar vs multipolar vs anaxonic vs pseudounipolar 4- Motor neurons vs interneurons vs sensory neurons 5- Generation of the neural impulse 6- The synaptic transmission 7- Propagation of the neural impulse  In myelinated neurons, the action potential propagation occurs via saltatory conduction, where the action potential "jumps" between nodes of Ranvier, increasing conduction speed. Outer and inner hair cells 1- Outer hair cells (OHCs) 2 5 1. Nucleus 2. Stereocilia 1 3. Cuticular plate 4 3 4. Medial efferent ending 5. Spiral afferent ending  The human cochlea contains approximately 12,000 outer hair cells at birth, and these cells are critical for amplifying sound stimuli. Each outer hair cell has several key components: the nucleus at the center, and the stereocilia at the top, which are responsible for detecting sound vibrations. The cuticular plate provides structural support, ensuring the cell's stability. The outer hair cells are typically arranged in a V-shape within the cochlea. Outer and inner hair cells 1- Outer hair cells (OHCs)  Outer hair cells are laterally cupped by outer phalangeal or Deiters cells (OPC/DC). Efferent fibers (E) from the medial olivocochlear (MOC) system form multiple connections at the base of the outer hair cell and are apposed by sub-synaptic cisternae (SSC). Outer hair cells also have afferent connections, where they synapse with the peripheral process of type II spiral ganglion cells (SGC) Outer and inner hair cells 1- Outer hair cells (OHCs) 2- Inner hair cells (IHCs) 2 1 1. Nucleus 4 2. Stereocilia 3. Cuticular plate 3 4. Radial afferent ending 5. Lateral efferent ending 5  The human cochlea contains approximately 3,500 inner hair cells at birth. Similar to outer hair cells, inner hair cells have stereocilia at the apex, which are responsible for detecting sound vibrations. The cuticular plate provides structural support, while the base of the cell shows the endings of radial and lateral afferent neurons, indicating the pathway for transmitting sensory information to the brain. Unlike outer hair cells, inner hair cells are arranged in a more linear fashion. Outer and inner hair cells 1- Outer hair cells (OHCs) 2- Inner hair cells (IHCs)  Inner hair cells are surrounded by inner phalangeal cells (IPC). At the base of the inner hair cell, there are ion channels, including voltage- sensitive calcium channels and Ca2+ activated K+ channels, which are essential for the electrochemical processes that occur during sound detection. The afferent connection (A) is made to the peripheral process of Type I spiral ganglion cells (SGC), which transmit sound information to the brain. The efferent (E) connection is made by the LOC system and is largely onto the afferents. Outer and inner hair cells 1- Outer hair cells (OHCs) 2- Inner hair cells (IHCs) 3- Synaptic ribbon  The synaptic ribbon is a specialized structure found at the active zone of the synapse. Positioned just a few nanometers away from the pre- synaptic membrane, the ribbon tethers hundreds of synaptic vesicles that are responsible for releasing glutamate. Research suggests that the primary function of the ribbon synapse is to enable the rapid processing of auditory information, allowing for quick and precise signaling to the brain. Outer and inner hair cells 1- Outer hair cells (OHCs) 2- Inner hair cells (IHCs) 3- Synaptic ribbon  Genetic mutations affecting the synaptic ribbon have a profound impact on auditory responses. Compared to wildtype mice, mutated mice show a decrease in both the peak rate and the adapted rate ratio in response to tone stimuli (Graph A). Additionally, they exhibit delayed peak latency and a reduced peak rate in response to click stimuli (Graph B), and a significantly lower peak rate to click, pip, and tone stimuli. These findings suggest that mutations affecting the synaptic ribbon result in a loss of response variation across different sound signals, which is essential for encoding the distinct transient features of auditory stimuli The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role The afferent pathway is responsible for transmitting auditory information from the cochlea to the brain for processing and perception It enables the detection and interpretation of sound stimuli, playing a crucial role in hearing Afferent fibers carry sensory signals from the cochlea, ultimately reaching the auditory cortex, where sound is processed and perceived The afferent (=ascending) pathway AFFERENT PATHWAY Two types of auditory 1- Role 2- Afferent fibers afferent neurons Bipolar, myelinated Type I Auditory Neurons (correspond to inner radial fibers connected to IHCs) About 30,000 afferent neurons in human 95% are Type I  There are two type of auditory afferent neurons. Type I afferent fibers are large, myelinated bipolar neurons that form synapses with the inner hair cells (IHCs). Each IHC is typically innervated by multiple Type I afferent fibers. Type I neurons are the dominant neurons in the auditory nerve, responsible for transmitting most of the sensory input. The afferent (=ascending) pathway AFFERENT PATHWAY Two types of auditory 1- Role 2- Afferent fibers afferent neurons Bipolar, myelinated Pseudomonopolar, unmyelinated Type I Auditory Neurons Type II Auditory Neurons (correspond to inner radial (correspond to outer spiral fibers connected to IHCs) fibers connected to OHCs) Only 5% of afferent neurons are Type II  Type II neurons are much less numerous, constituting around 5% of the auditory nerve fibers. Type II fibers are smaller and unmyelinated pseudomonopolar neurons that primarily synapse with the outer hair cells (OHCs) The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei Inferior colliculus Nucleus of lateral lemniscus Superior olivary complex Cochlear nuclei CN VIII COCHLEA  The cochlear nuclei are the first relay station for auditory information after the cochlea. Located at the brainstem, these nuclei receive input from the afferent fibers that come from the inner hair cells. The cochlear nuclei play a crucial role in processing sound information and are directly involved in generating Wave II of the auditory brainstem response (ABR), which is represented in the graph on the right.. The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei 3.2- Superior olivary complex Inferior colliculus Nucleus of lateral lemniscus Superior olivary complex Cochlear nuclei CN VIII COCHLEA  Next, the auditory signal moves from the cochlear nuclei to the superior olivary complex (SOC), located further up in the brainstem. The SOC is believed to be responsible for binaural processing, which helps in sound localization by comparing the signals from both ears. This structure is essential for generating Wave III of the ABR, which you can see in the graph. The Wave III response reflects the involvement of the SOC in processing sound information and its role in determining directionality and timing of sound signals. The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei 3.2- Superior olivary complex Inferior colliculus 3.3- Lateral lemniscus Nucleus of lateral lemniscus Superior olivary complex Cochlear nuclei CN VIII COCHLEA  After passing through the superior olivary complex, the auditory signal continues to the nucleus of the lateral lemniscus (NLL). The NLL is believed to play a key role in processing auditory information related to the intensity and timing of sound, further refining the signals before they reach the next relay station. Wave IV of the ABR is generated by this structure, as shown in the graph, and it reflects the complex processing of sound in the brainstem, particularly related to the temporal aspects of auditory signals. The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei 3.2- Superior olivary complex Inferior colliculus 3.3- Lateral lemniscus 3.4- Inferior colliculus Nucleus of lateral lemniscus Superior olivary complex Cochlear nuclei CN VIII COCHLEA  Following the nucleus of the lateral lemniscus, the auditory information is sent to the inferior colliculus, which serves as a major integration center for auditory signals. The inferior colliculus is believed to process complex auditory information, such as frequency and spatial cues. It is involved in generating Wave V of the ABR, as depicted in the graph. The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei 3.2- Superior olivary complex Inferior colliculus 3.3- Lateral lemniscus 3.4- Inferior colliculus Nucleus of lateral lemniscus 3.5- Medial geniculate body Superior olivary complex Cochlear nuclei CN VIII COCHLEA  Beyond the inferior colliculus, the auditory information travels to the medial geniculate body (MGB) of the thalamus, which serves as a relay station for the auditory cortex. The afferent (=ascending) pathway AFFERENT PATHWAY Auditory cortex 1- Role 2- Afferent fibers 3- Afferent structures Medial geniculate nucleus 3.1- Cochlear nuclei 3.2- Superior olivary complex Inferior colliculus 3.3- Lateral lemniscus 3.4- Inferior colliculus Nucleus of lateral lemniscus 3.5- Medial geniculate body 3.6- Auditory cortex Superior olivary complex Cochlear nuclei CN VIII COCHLEA  Finally, the auditory information reaches the auditory cortex, where higher-level processing occurs, such as speech recognition and music processing. Both the thalamus and the auditory cortex contribute to auditory evoked potentials with middle latency (between 10 and 80 ms) and late latency (greater than 80 ms). These responses consist of a series of positive and negative waves with larger amplitudes, originating from the thalamus, the primary and secondary auditory cortices, and the associative cortex. The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures 3.1- Cochlear nuclei 3.2- Superior olivary complex 3.3- Lateral lemniscus 3.4- Inferior colliculus 3.5- Medial geniculate body 3.6- Auditory cortex 4- Neurotransmitters Glutamate: Excitatory, transmits sound signals  The afferent pathway in the auditory system primarily relies on glutamate as the neurotransmitter to transmit auditory signals from the cochlea to the brain. In inner hair cells, glutamate is released at the synaptic ribbon to communicate with type I afferent neurons from the spiral ganglion cells. Although outer hair cells do not have synaptic ribbons, they still contain glutamate vesicles that are released at synapses with type II afferent neurons from the spiral ganglion cells. The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures Auditory Brainstem Responses 3.1- Cochlear nuclei 3.2- Superior olivary complex 3.3- Lateral lemniscus 3.4- Inferior colliculus 3.5- Medial geniculate body 3.6- Auditory cortex 4- Neurotransmitters 5- Afferent pathway evaluation  Several techniques are available to evaluate the function of the afferent pathway. One of the most common is the Auditory Brainstem Response (ABR), which allows us to assess the integrity of the entire auditory pathway from the cochlea to the brainstem The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures Auditory Brainstem Responses 3.1- Cochlear nuclei 3.2- Superior olivary complex 3.3- Lateral lemniscus Middle and Late Latency Evoked 3.4- Inferior colliculus Responses 3.5- Medial geniculate body 3.6- Auditory cortex 4- Neurotransmitters 5- Afferent pathway evaluation Middle and Late Latency Evoked Responses can be used to assess the functionally at higher levels, including the thalamus and auditory cortex The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures Auditory Brainstem Responses 3.1- Cochlear nuclei 3.2- Superior olivary complex 3.3- Lateral lemniscus Middle and Late Latency Evoked 3.4- Inferior colliculus Responses 3.5- Medial geniculate body 3.6- Auditory cortex Electrocochleography 4- Neurotransmitters 5- Afferent pathway evaluation  Lastly, Electrocochleography can be used us to measure the electrical potentials generated by the cochlea and the auditory nerve in response to acoustic stimulation and assess whether the early structure of the afferent pathway are functioning properly The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures 3.1- Cochlear nuclei 3.2- Superior olivary complex Acoustic Neuroma 3.3- Lateral lemniscus 3.4- Inferior colliculus 3.5- Medial geniculate body 3.6- Auditory cortex 4- Neurotransmitters 5- Afferent pathway evaluation 6- Pathophysiological examples  In patients with acoustic neuroma, conduction time is typically prolonged between Waves I and III due to compression of the auditory nerve. The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures 3.1- Cochlear nuclei 3.2- Superior olivary complex Acoustic Neuroma 3.3- Lateral lemniscus 3.4- Inferior colliculus Brainstem lesions 3.5- Medial geniculate body 3.6- Auditory cortex 4- Neurotransmitters 5- Afferent pathway evaluation 6- Pathophysiological examples  In cases of isolated brainstem lesions, the conduction delay is typically seen between Waves III and V. The afferent (=ascending) pathway AFFERENT PATHWAY 1- Role 2- Afferent fibers 3- Afferent structures 3.1- Cochlear nuclei 3.2- Superior olivary complex Acoustic Neuroma 3.3- Lateral lemniscus 3.4- Inferior colliculus Brainstem lesions 3.5- Medial geniculate body 3.6- Auditory cortex Demyelinating Pathologies 4- Neurotransmitters 5- Afferent pathway evaluation 6- Pathophysiological examples  In patients with demyelinating pathologies, such as multiple sclerosis or neuropathy, Waves IV and V may exhibit reduced amplitude or be absent due to disruption of nerve conduction in the brainstem. Coding Mechanisms in the Auditory Pathway 1- Temporal Coding Theory  Receptor potentials generated by hair cells in the cochlea provide insight into temporal coding. For pure tones below 3 kHz, the receptor potential oscillates in synchrony with each cycle of the sound wave, following the waveform of the stimulus with remarkable precision. Coding Mechanisms in the Auditory Pathway 1- Temporal Coding Theory  At higher frequencies, however, this phase-locking ability diminishes. The receptor potential no longer oscillates with each cycle of the stimulus and instead shifts to a steady direct current, or DC offset. Coding Mechanisms in the Auditory Pathway 1- Temporal Coding Theory 2- Tonotopic Coding Theory Corresponds to Corresponds to apex of the cochlea base of the cochlea Primary auditory Secondary cortex auditory cortex  Since the Temporal Coding Theory is limited in its ability to explain how high-frequency sounds are processed, another mechanism must account for this. This leads us to the Tonotopic Coding Theory. In the cochlea, sound frequencies are mapped along its length, with high frequencies represented at the base and low frequencies at the apex. This organization arises from the mechanical properties of the basilar membrane, which vary along its length and allow different regions to respond maximally to different frequencies. This tonotopic arrangement is preserved throughout the auditory pathway and extends to the primary auditory cortex, where neurons are organized in a frequency-specific map. Coding Mechanisms in the Auditory Pathway 1- Temporal Coding Theory 2- Tonotopic Coding Theory 3- Intensity Coding Theory  Sound intensity is encoded by the auditory system through the activity of auditory nerve fibers. Each fiber has a specific frequency tuning curve, as seen in the first panel. These curves show the range of frequencies to which a fiber is responsive, along with the minimum sound intensity required to increase its firing rate above the spontaneous firing level. The lowest point on the curve represents the fiber’s characteristic frequency, where it is most sensitive to sound. As sound intensity increases, more auditory nerve fibers are recruited to respond. This is because louder sounds not only stimulate fibers tuned to their characteristic frequency but also activate fibers with nearby tuning curves. This recruitment results in an increase in the overall firing rate of the auditory nerve and provides a robust code for intensity. The efferent (=descending) pathway Modulates auditory input by controlling cochlear EFFERENT PATHWAY amplification 1- Role Provides protection against acoustic trauma and noise-induced damage Enhances signal detection in noisy environments through selective attention  The efferent pathway plays a critical role in modulating auditory input. By controlling the activity of outer hair cells, it adjusts cochlear amplification, effectively fine-tuning our sensitivity to sound. This modulation is particularly important in protecting the ear from acoustic trauma and noise-induced damage by reducing excessive stimulation in loud environments. Additionally, the efferent system improves signal detection in noisy environments, aiding selective attention to important auditory cues, such as focusing on a conversation in a crowded room. The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops  The efferent auditory network consists of multiple feedback loops that connect different regions of the auditory system. Olivocochlear neurons in the superior olivary complex (SOC) receive direct projections from both the inferior colliculus (IC) and the auditory cortex (AC), but not from the medial geniculate body (MGB). Similarly, cochlear nucleus (CN) neurons also receive direct input from the IC and AC, forming a comprehensive feedback network. The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle  The uncrossed olivocochlear bundle (uncrossed OCB) originates primarily from the ipsilateral side of the superior olivary complex (SOC) and terminates in the cochlea. A majority of uncrossed OCB neurons are small and originate bilaterally. These neurons predominantly innervate inner hair cells (IHCs) rather than outer hair cells (OHCs). This schematic illustrates the origins and terminations of the uncrossed OCB, emphasizing its ipsilateral dominance and the contribution of small neurons. These neurons play a significant role in modulating the afferent input at the level of the IHCs. The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle 4- Crossed olivocochlear bundle  The crossed olivocochlear bundle (crossed OCB), in contrast to the uncrossed OCB, predominantly originates from the contralateral side of the superior olivary complex (SOC). This bundle largely targets the outer hair cells (OHCs), which are crucial for cochlear amplification. The schematic demonstrates the pathways of the crossed OCB, highlighting its contribution from large neurons and its significant innervation of OHCs. This organization enables the crossed OCB to exert inhibitory control over OHC motility, effectively modulating cochlear sensitivity and protecting the ear from overstimulation. The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle 4- Crossed olivocochlear bundle 5- Neurotransmitters LOC MOC Dopamine Acetylcholine GABA  The efferent system relies on distinct neurotransmitters depending on the type of olivocochlear fibers. The medial olivocochlear (MOC) fibers, which innervate outer hair cells (OHCs), predominantly use acetylcholine as their neurotransmitter. Acetylcholine has an inhibitory effect, reducing OHC motility and controlling cochlear amplification. On the other hand, lateral olivocochlear (LOC) fibers, which target afferent nerve fibers near inner hair cells (IHCs), primarily use dopamine and GABA. These neurotransmitters modulate afferent signal strength and provide a protective role by reducing excitotoxicity under conditions of excessive stimulation. The efferent (=descending) pathway EFFERENT PATHWAY Otoacoustic Emissions 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle 4- Crossed olivocochlear bundle 5- Neurotransmitters 6- Efferent pathway evaluation  In clinical audiology, the function of the efferent auditory pathway can be evaluated using several techniques. Otoacoustic Emissions (OAEs), which measure sound generated by outer hair cells in response to auditory stimuli, are particularly useful because their amplitude can be modulated by efferent system activity, especially when contralateral sound stimulation is applied The efferent (=descending) pathway EFFERENT PATHWAY Otoacoustic Emissions 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle Acoustic Reflex Thresholds and 4- Crossed olivocochlear bundle Decay 5- Neurotransmitters 6- Efferent pathway evaluation  Acoustic Reflex Thresholds and Decay, which assess the stapedius muscle’s response to sound, provide indirect information about efferent function in the lower brainstem and are valuable in detecting abnormalities in the reflex arc. The efferent (=descending) pathway EFFERENT PATHWAY Otoacoustic Emissions 1- Role 2- Several feedback loops 3- Uncrossed olivocochlear bundle Acoustic Reflex Thresholds and 4- Crossed olivocochlear bundle Decay 5- Neurotransmitters 6- Efferent pathway evaluation Middle Ear Muscle Reflex  The Middle Ear Muscle Reflex, or MEMR, which involves measuring changes in middle ear impedance in response to loud sounds, helps evaluate the protective role of the efferent pathway in managing high-intensity stimuli. The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops Hyperacusis and Tinnitus 3- Uncrossed olivocochlear bundle 4- Crossed olivocochlear bundle 5- Neurotransmitters 6- Efferent pathway evaluation 7- Pathophysiological examples  It is not yet fully understood which exact structures and mechanisms are responsible for tinnitus and hyperacusis. However, both conditions are believed to be linked to dysregulation in the efferent pathway, specifically at the level of the Medial Olivocochlear (MOC) system. The MOC system plays an important role in regulating cochlear activity and auditory sensitivity. When it is not functioning properly, the impaired modulation of auditory input may trigger compensatory mechanisms in the brain that contribute to the onset of tinnitus and hyperacusis. For tinnitus, evidence suggests that a compromised MOC pathway disrupts the feedback control of neural activity in the cochlea, potentially leading to aberrant neural firing in the auditory nerve. This misfiring may be perceived by the brain as phantom sounds, or tinnitus. In the case of hyperacusis, the lack of proper modulation may cause the brain to perceive everyday sounds as unusually loud or uncomfortable due to increased sensitivity The efferent (=descending) pathway EFFERENT PATHWAY 1- Role 2- Several feedback loops Hyperacusis and Tinnitus 3- Uncrossed olivocochlear bundle 4- Crossed olivocochlear bundle Increased Susceptibility to Noise- 5- Neurotransmitters Induced Hearing Loss 6- Efferent pathway evaluation 7- Pathophysiological examples  Another case where the efferent pathway plays a critical role is in noise- induced hearing loss. The MOC system and middle ear reflexes both function to reduce cochlear gain and attenuate intense sound stimuli— effectively protecting the cochlea from potential damage due to loud noise exposure. The MOC system specifically acts by decreasing the sensitivity of the outer hair cells, which are responsible for amplifying sound in the cochlea. When the MOC system or middle ear reflexes are compromised, the cochlea is no longer able to suppress loud sounds effectively. This lack of protection makes individuals more susceptible to damage from noise, as there is no longer an efficient mechanism to reduce the input or protect the cochlear structures. So, without these feedback mechanisms, exposure to high-intensity sounds can result in permanent cochlear damage and hearing loss. Recap of Today’s Learnings Recap of Today's Learnings (1/2) Neurons are specialized cells that transmit electrical impulses throughout the body Myelination increases conduction speed in neurons, enhancing communication efficiency Different neuron types (unipolar, bipolar, multipolar, pseudounipolar) serve distinct roles in the nervous system The afferent pathway transmits sensory information from the cochlea to the auditory cortex, passing through several key structures Recap of Today’s Learnings Recap of Today's Learnings (2/2) Neurotransmitters, including glutamate, play a crucial role in transmitting signals within the afferent pathway Sounds are encoded in the auditory system primarily through tonotopic coding, where different frequencies activate specific regions along the cochlea The intensity of sounds is coded by the recruitment of additional auditory nerve fibers and the increase in their firing rates The efferent pathway provides feedback to the cochlea, helping protect the ear and modulate auditory input