Neurological Diseases Part II

Questions and Answers

What is a primary structural feature of the cortico-thalamo-cortical circuitry involved in typical absence seizures?

VPM neurons solely operate in tonic firing mode.

nRT neurons provide feedback inhibition to excitatory VPM neurons. (correct)

VPM inhibitory neurons project to excitatory neurons in the cortex.

Excitatory connections exclusively exist within the thalamic nuclei.

In typical absence seizures, what change does unilateral inhibition of somatosensory cortex GABA receptors produce?

It causes tonic-mode firing in all thalamic neurons.

It activates bilateral SWDs only in the thalamus.

It significantly reduces spike-wave discharges (SWDs).

It produces spike-wave discharges (SWDs). (correct)

Which mutation is specifically associated with Dravet syndrome?

GARRG2 mutation

SCN1A mutation (correct)

GABRB3 mutation

GABRA1 mutation

What physiological state is characterized by the burst-mode firing of VPM neurons in non-epileptic individuals?

Low-frequency delta activity Signup and view all the answers

What is the role of GABA receptors in the central nervous system (CNS)?

They are involved in most synaptic inhibition. Signup and view all the answers

Which region is NOT typically involved in the activation during generalized epileptic seizures?

Mediobasal temporal lobe Signup and view all the answers

Mutations affecting which type of protein are often linked to IGE syndromes?

Synaptic proteins Signup and view all the answers

How does increased tonic GABA inhibition in nRT affect SWDs?

It reduces or eliminates SWDs. Signup and view all the answers

Which of the following describes the firing modes of VPM neurons?

Both tonic and bursting firing modes are present. Signup and view all the answers

What is the primary outcome of high-resolution electrophysiological recordings in CAE animal models?

Understanding of cortical and thalamic interactions. Signup and view all the answers

Study Notes

Neurological Diseases and Seizures

Seizures are brief, spontaneous neurological events caused by excessive and synchronized brain activity.
Types of seizures include typical absence seizures, focal impaired awareness seizures (FIAS), and tonic-clonic seizures, each activating different brain circuits.

Typical Absence Seizures

Engages widespread regions across both cerebral hemispheres rapidly, reflecting immediate cortical activation.
Functional imaging techniques (fMRI, MEG, high-density EEG) show that these seizures primarily involve the thalamus, frontal, and parietal cortices.
In animal models, they activate specific cortical and thalamic areas, including the somatosensory barrel cortex and thalamic nuclei (nRT and VPM).

Cortico-Thalamo-Cortical (CTC) Circuitry

CTC circuitry has three significant features promoting oscillations:
- Excitatory VPM neurons project to inhibitory GABAergic neurons in nRT, which inhibit VPM, creating feedback.
- VPM shows two firing modes: tonic and bursting.
- High interconnectivity exists between VPM and nRT neurons within and across thalamic nuclei.

Absence Seizure Mechanisms

In non-epileptic individuals, VPM burst-mode firing contributes to delta activity during deep sleep and high-frequency sleep spindles.
Research identifies conditions that lead this oscillating circuit to produce pathological spike-wave discharges (SWDs) during absence seizures.
In CAE animal models, SWD spikes originate in the somatosensory cortex and rapidly spread to the thalamus.

GABA and Seizure Phenomena

Inhibition of somatosensory cortex GABA receptors can induce SWDs, while action potential blockade in this region abolishes bilateral SWDs.
Increased GABA inhibition in nRT reduces or eliminates SWDs, whereas bilateral GABA antagonists promote them.
Tonic hyperpolarization in VPM increases SWDs, but synaptic GABA signaling facilitation does not affect them.

Genetic Factors in Seizures

Typical absence seizures commonly occur in patients with idiopathic generalized epilepsy (IGE), which lack gross anatomical lesions.
IGE syndromes are often monogenic, involving familial or de novo mutations in synaptic protein genes impacting neurotransmitter receptors and ion channels.
Specific gene mutations associated with absence seizures include:
- GABRA1, GABRB3, and GARRG2 for childhood absence epilepsy (CAE).
- SCN1A mutations linked to Dravet syndrome.
GABA receptors, primarily chloride-selective ion channels responsible for CNS inhibition, are heteropentamers composed mainly of two alpha subunits among various combinations of receptor subunits.

Description

Explore the pathophysiology and mechanisms behind neurological diseases, focusing on seizures. Understand the different types of seizures and their brain circuit activations. This quiz covers essential knowledge for students in neurology or related medical fields.