SENSORY SYSTEMS - APPLIED PHARMACOLOGY

Question 1

What is tinnitus? = 2

Answer 1

1. Tinnitus is the SENSORY PERCEPTION OF SOUND WHEN THERE IS NO CORRESPONDING EXTERNAL SOUND IS PRESENT
2. • It is associated with TRAUMA TO THE AUDITORY PATHWAY

Question 2

Peripheral auditory pathway - OUTER EAR ANATOMY AND PATHWAY

Answer 2

• Anatomy: auricle/pinna, ear canal to ear drum
• Function: amplification for specific frequencies

Question 3

Peripheral auditory pathway - MIDDLE EAR ANATOMY AND PATHWAY

Answer 3

Anatomy: malleus, incus, stapes

• Function: transfer of sounds from AIR WAVEs to
  FLUID WAVES

Question 4

Peripheral auditory pathway - INNER EAR ANATOMY AND PATHWAY

Answer 4

Anatomy: cochlea

• Function: hearing transduction

Question 5

Peripheral sense organ:

Answer 5

the cochlea

shaped like a spiral,

• is a vital part of the inner ear responsible for hearing.
• It has three fluid-filled sections: the scala vestibuli, scala media, and scala tympani.

1. Basilar Membrane: This stretchy membrane inside the cochlea helps convert sound vibrations into electrical signals.
2. Hair Cells: These tiny cells on the basilar membrane transform mechanical vibrations into electrical signals, which then travel to the brain through the auditory nerve.
3. Organ of Corti: Located on the basilar membrane, this structure contains the hair cells and supporting cells crucial for hearing.
4. Auditory Nerve: Nerve fibers from the hair cells form the auditory nerve, transmitting electrical signals to the brainstem for processing.
5. In short, the cochlea turns sound waves into signals the brain can understand, making it essential for hearing
6. The semicircular canals are responsible for detecting rotational movements of the head and are crucial for balance and spatial orientation.

Question 6

Central auditory pathway = 6

Answer 6

1. • Auditory Nerve
2. • Cochlear Nucleus (Brainstem)
3. • Superior Olivary Nucleus (Brainstem)
4. • Inferior Colliculus (Brainstem)
5. • Medial Geniculate Nucleus (Thalamus)
6. • Primary Auditory Cortex (Cortex)

Question 7

There are many types of possible trauma to the auditory pathway…

a common consequence

Answer 7

is hearing loss

Question 8

Cochlear trauma

Answer 8

1. ACOUSTIC TRAUMA
2. PHSYICLA TRAUMA
3. INFECTIONS
4. AGING
5. CHEMICAL EXPOSURE
6. ALL PRODUCE COCHLEAR TRAUMA -Hair cells are sensory cells located along the basilar membrane of the cochlea and are essential for hearing. They detect sound vibrations and convert them into electrical signals that are sent to the brain via the auditory nerve.

Question 9

EXPLAIN WHAT HEARING LOSS IS: 4

Answer 9

1. • Hearing loss is a spectrum.
2. • Some people are profoundly deaf,
3. while others are unable
   to hear only specific
   frequencies.
4. • Hearing loss can be treatable in some cases

Question 9

What is the relationship between hearing loss and tinnitus, and what are some common causes of hearing loss?

Additionally, explain the peripheral deafferentation theory of tinnitus.

Answer 9

1. • Hearing loss is commonly associated with
     tinnitus
2. • Evidence: Tinnitus sufferers will often match the sound of their tinnitus to their hearing loss.
3. • Hearing loss is a commonly consequence
     of aging, loud noise exposure, infection, eardrum rupture
4. • Tinnitus theory of peripheral deafferentation

Question 10

Tinnitus theory of peripheral deafferentation: 4

Answer 10

1. Peripheral deafferentation means reduced sensory input from the cochlea.
2. In tinnitus, damage to the cochlea’s hair cells leads to fewer signals sent to the brain.
3. This can cause the brain to create phantom sounds, like ringing or buzzing.
4. So, tinnitus might be linked to hearing damage in the cochlea.

Question 11

Explain the ‘central auditory responses’ associated with cochlear trauma = 3

Answer 11

1. Neural Hyperactivity: More activity in the auditory nerve and brain pathways makes tinnitus sounds louder.

• Heightened nerve activity in the inferior colliculus, a part of the midbrain involved in auditory processing.

2. Changes in Neural Synchrony: Signals in the auditory system get mixed up, making tinnitus worse.
3. Changes in Tonotopic Organization: The brain’s map of sound frequencies gets jumbled, making tinnitus sounds weirder.

Question 12

Approaches for investigating tinnitus = 5

Answer 12

Multiple ways to investigate:
1. Anatomical,
2. Molecular,
3. Pharmacological,
4. Psychology,
5. Physiological

Question 13

What are the primary approaches for investigating tinnitus, particularly focusing on

‘electrophysiology and neuropharmacology?’

Answer 13

1. involve electrophysiology and neuropharmacology.
2. These approaches ‘aim to modulate two key aspects of tinnitus’:

—- 1. Modulating hyperexcitability.

—– 2. Modulating hyperactivity.

Question 14

How can drugs affect hair cell ion channels? = 3

Answer 14

1. Any drug that acts on a ‘specific ion channel’ can

….

2. ‘alter the membrane potential of hair cells’,

…

3. ‘potentially impacting their function.’

Question 15

Targeting Central Hyperexcitability ….through ‘furosemide’

= 7

Answer 15

1. Furosemide, a loop diuretic,
2. inhibits the Na-K-2Cl cotransporter in the stria vascularis.
3. This cotransporter maintains the endocochlear potential of the scala media.
4. When furosemide blocks the cotransporter,
5. it decreases the endocochlear potential,
6. impairs cochlear function, and
7. reduces the cochlear nerve’s spontaneous firing rate.

Question 16

If the central auditory response to cochlear damage alone can’t explain tinnitus, what else might contribute to the neural substrate for tinnitus?

Answer 16

1. while the central auditory response to cochlear damage consistently occurs,
2. tinnitus only manifests in 20-40% of cases of hearing loss.
3. Therefore, other factors beyond cochlear damage, such as alterations in neural activity and connectivity in networks associated with attention, emotion, and memory, may contribute to the neural substrate for tinnitus.

Question 17

Neural Substrate of Tinnitus

Answer 17

Structural abnormalities have been observed in several brain regions, including the

1. cingulate
2. prefrontal cortex,
3. parahippocampus,
4. amygdala,
5. insula,

in individuals with tinnitus.

These structural abnormalities suggest involvement of regions associated with emotion, memory, attention, and sensory processing in the neural substrate of tinnitus

Question 18

What is the Dysfunctional Gating Theory of Tinnitus? = 2

Answer 18

The Dysfunctional Gating Theory of Tinnitus suggests…

1. that tinnitus arises from an IMBALANCE IN NEURAL GATING MECHANISMS WITHIN THE AUDITORY SYSTEM
2. ALLOWING ABNORMAL NEURAL ACTIVITY TO PASS THROUGH UNCHECKED, RESULTING IN THE PERCEPTION OF TINNITUS

Question 19

Targeting Hyperactivity… 2 AND EXPLAIN

Answer 19

1. Inhibitory Gating: Inhibitory mechanisms regulate neural activity along the auditory pathway, potentially preventing hyperactivity from reaching the auditory cortex.
2. Preventing Hyperactivity: Modulating inhibitory transmission within this circuitry may prevent hyperactivity from developing.

…..By targeting inhibitory mechanisms, it’s possible to regulate the flow of neural signals in the auditory pathway, potentially mitigating hyperactivity associated with conditions like tinnitus.

Question 20

How does the auditory cortex regulate hyperactivity,

and what role do GABA receptors play? = 3

Answer 20

1. The auditory cortex utilizes local GABA interneurons to provide inhibitory input,
2. regulating hyperactivity. Gaboxadol, a GABA agonist, acts on GABA receptors,
3. potentially modulating hyperactivity and reducing tinnitus symptoms…Inhibitory transmission

Question 21

Tinnitus and Hearing Loss

Answer 21

Tinnitus is a phantom perception of sound, strongly linked to hearing loss.

Question 21

how did GABA receptor inhibitors affect tinnitus behaviors compared to ketamine? = 2

Answer 21

1. GABA receptor inhibitors like Vigabatrin/NO711 abolished ‘tinnitus behaviors by INCREASING GABA-mediated INHIBITION’.
2. However, ketamine, an ‘NMDA receptor antagonist’, did not abolish behavioural signs of tinnitus.

Question 22

Peripheral Deafferentation and Central Auditory Changes

Answer 22

Following cochlear trauma, peripheral deafferentation occurs, leading to central auditory neural changes such as hyperexcitability and hyperactivity.

Question 23

Modulating Neuronal Activity with Ion Channel Drugs

Answer 23

Ion channel drugs can modulate neuronal activity that develops as a result of cochlear trauma.

Question 24

Using Inhibitory Transmission Drugs to Modulate Neuronal Activity

Answer 24

Drugs targeting inhibitory transmission can be utilized to modulate neuronal activity associated with tinnitus.