Brain microcircuitry

Question 1

Inhibition in Neuronal Circuits

Answer 1

Recurrent inhibition: Activation of neuron → Activation of inhibiting interneuron
Feed-Forward inhibition: Activation of interneuron → Inhibiting excitatory neurons
Disinhibition: Activation interneuron → Inhibition of another interneuron → No more inhibition of the excitatory neuron

Question 2

Spinal cord reflex arc

Answer 2

DRG neurons synapse on dorsal horn neurons, project in brain
Can also form reflex arc to directly relay excitation onto ventral horn neurons
Alpha Motorneurons → Neg. Feedback loop by causing cholinergic activation of Renshaw cells (= Recurrent inhibition)

Question 3

Structure & Pathway of the hippocampus

Answer 3

Dentate gyrus (3 layers) & Cornu ammonis (CA1-3)
Enthorhinal cortex → Dentate gyrus → Mossy fibers → CA3 → Schaffer colaterals → CA1

Question 4

Long Term Potentiation

Answer 4

Increased synaptic strength following high-frequency stimulation of a chemical synapse

AP → AMPAR activation + Na+ influx → EPSP
Increased AP frequency → Depolarization → Mg2+ dissociate from NMDAR → Ca2+ influx → Calmodulin activation → CaMKII activation → Phosphorylates AMPARs → Increased conductance

Late phase: c-AMP dependent kinases phosphorylate TF CREB → Binds to CRE promotor → Increased synthesis of AMPARs, incorporated in Membrane

Question 5

Basal ganglia

Answer 5

Interconnected subcortical nuclei
Facilitation of voluntary movement & simulatenous inhibition of competing movements

Striatum: Caudate nucleus & Putamen
Globus pallidus: Internal & external (GPi & GPe)
Substantia nigra: Pars compacta (SNc) & Pars reticulata (SNr)
Subthalamic nucleus (STN)

Question 6

Basal ganglia microciruitry (Direct pathway)

Answer 6

Motor cortex activates D1 in Striatum → GABA release to GPi & SNr → Less inhibition of the Thalamus → Activation + Positive Feedback

Question 7

Basal ganglia microcircuitry (Indirect pathway, Glutamate)

Answer 7

Motor cortex activation leads to activation of D2 in Striatum → Inhibition of the GPe → No longer inhibition of the STN → Activation leads to activation of GPi & SNR → Inhibit Thalamus → Less activity in Thalamus

Question 8

Basal ganglia microcircuitry (Indirect pathway, Dopamine)

Answer 8

Motor cortex activation & Activation of SNc → Less D2 activation in the Striatum → GPe more active → Inhibition of STN & GPi & SNR → Increased activity in Thalamus + Positive Feedback loop

Question 9

Striatum Structure

Answer 9

Ventral: Ncl. Accumbens & olfactory tubercle
Dorsal: Caudate nucleus & Putamen

Question 10

Striatum cells

Answer 10

Medium spiny neurons (MNS = SPNs) → GABAergic projection neurons
ISPNs: Indirect pathway → Inhibit motor circuits
DSPNs: Direct pathway → Disinhibit motor circuits

ChAT+ interneurons: Large & aspiny, tonically active
GABAergic interneurons: Fast spiking (FSI) & low threshold spiking (LTS)

Question 11

Somatosensory pathways

Answer 11

Pain, temperature & coarse touch cross in the midline in the spinal cord
Fine touch, proprioception & vibration cross midline in medulla
Sensory pathways synapse in Thalamus, sensation perceived in primary somatic sensory cortex

Question 12

Mechanoreceptors of the Skin (Fibers)

Answer 12

C-Fibers → Temperature & force sensing, project in epidermis
Adelta-Fibers → Important for pain & fast stimuli, project in dermis
Project to low-threshold mechanoreceptors (LTMRs), further in dorsal horn

Question 13

Nociception receptors & pathways

Answer 13

= Objective detection & processing of noxious stimuli
Receptors: TRPM8 = Cold, TRPV1 = Heat, ASIC: Chemical, Piezo-/TREK-1: Mechanical
Pathway: Perception in Epidermis → Conduction through Dermis → Nociceptor → DRG → Spinal neurons

Question 14

Noxius stimulation

Answer 14

Inflammatory soup, K+, ATP → Nociceptor stimulation → Antidromic axon reflexes lead to secretory vesicles containing neuropeptides

Substance P → Increases permeability of capillary walls → Edema (Tumor)
CGRP → Relaxes smooth vascular musculature → Vasodilatation & Blood flow (Rubor, Calor)
→ Both degranulate mast cells → Histamine release → Neurogenic inflammation

Question 15

Gate control theory

Answer 15

Non-painful sensations can over-ride & reduce painful sensations → e.g. Opiate receptor activaition, interneuron activation, serotonin release…

Question 16

Pathological pain

Answer 16

Hyperalgesia: Painful stimulation induces excessively strong pain sensation
Allodynia: Normally non-painful stimuli are perceived as painful
Resting pain: Spontaneous pain without mechanical/thermal stimulation

Question 17

Merkel corpuscule

Answer 17

Merkel corpuscule: Slow adapting (SA1), epidermis, small receptor field → Free nerve ending in contact with modified endothelial cell → For light perpendicular touch

Question 18

Ruffini corpuscule

Answer 18

Ruffini corpuscle: SA2, Dermis, large receptor field → Free nerve ending in contact with collagen-fibers → Tangential stretching of the skin

Question 19

Meissner corpuscule

Answer 19

Meissner corpuscle: Rapidly adapting (RA), hairless skin, small receptive fields → Lamellar arranged Schwann cells → Low frequency vibrations

Question 20

Pacinian corpuscule

Answer 20

Pacinian corpuscle: In subcutaneous skin, large receptive fields → Multiple layers of Schwann cells → High frequency vibrations