Nervensystem II: ausgewählte Kapitel

You have impaired social and communicative skills& repetitive behaviours

Converging problem: connectivity:

1. Decrease in connectivity between specific brain regions --> Hypoconnectivity (defective axon growth and guidance)
   1. Increase in connectivit within regions --> Hyperconnectivity (to many neurons, dendrites, spines -> lack of apoptosis)

1. Seizures induce changes in axon guidance proteins -> rewiring of neuronal circuits in later stages of epillepsy

2. recurrent seizures in the hippocampus -> new mossy fibre collaterals which abberrantly innervate the molecular layer and synapse with their own dendrites -> self-stimulation

1. Fissures generally form earlier than sulci and are often longer or deeper
2. Fissures --> formed by external forces
   1. include forces from within the ventricular system
3. Sulci --> formed by internal forces
   1. from within the parenchyma of the brain itself
   2. proliferation and growth of individual cells, neurons and glial processes

1. Interhemispheric fissure: divides the telencephalon into two hemispheres
2. hippocampal fissure: between the dentate gyrus and ammons horn
3. sylvian fissure
4. calcarine fissure: is on the medial side of the occipital lobe

Neural connectivity forms after the radial, inside out proliferation and migration of neurons. The connectivity begins in Layer 6 and goes inwards. 

The connectivity driven tangential growth mainly affects superficial layers and triggers the formation of gyri and sulci.

The SVZ is thicker at sites where gyri form and thinner where sulci will form. 

1. Holoprosencephaly: is the failure of the hemispheric fissure -> earliest cerebral defect.
2. Fetal Alcohol Syndrom:
   • most common retardation cause
   • changes in brain structures and behaviour:
     • Learning defecit
     • memory
     • executive functioning
   • microcephally

• Myelin sheath is generated by Oligodendrocytes
• does not occur before the growth cone reaches its final destination
• Timeline:
  • earliest myelination: 24 weeks of gestation
  • corticospinal tract: fully at 2 years
  • corpus callosum: late adolescence is when it finished
  • ipsilateral frontotemporal association bunlde: not until 32 years old (emotions and decisions)
• can be detected by MRI

1. Is the formation of synapses between individual neurons
2. it begins before the 27th week, but mainly occurs after birth
   1. happens at the same time as growth of axons and dendrites&myelination of axons in the subcortical white matter
3. Three Phases of Synaptogenesis:
   1. immature synapses form between axons and dendrites
   2. synapses convert from a silent to an active state
   3. reduction in the number of synapses -> refining of the neuronal connections within the circuit (Synaptic pruning)

= is the selective elimination of a portion of neurons and synapses -> allows us to become experts

Happens mainly at 3 times in our lives:

1. at two years of age (when we speak our first words)
2. Adolescence
3. at 40 years of age (midlife crisis).

• White matter: grows, becomes more extensive in volume
• Grey matter: reduces in volume

Primary areas(S1, M1): 

• They develop earlier
• in earlier childhood the genetic influence is larger

Dorsal/lateral PFC, temporal lobes:

• show greater genetic influence with maturation
• complex cognitive complexes are more heritable in adolescents
• IQ becomes increasingly heritable with maturity

In general, the cortical thickness decreases with age:

• superior intelligence: start with a relatively thin cortex, which increases and peaks at 11, and then decreases again
• average intelligence: steady decline in cortical thickness throughout.

Attention deficit and hyperactivity disorder: The development lags behind by several years

• The parietal lobe is most affected --> Attention deficit
• Exercise -> induces pruning and can help speed up the development

Men:

• intraparietal sulcus and inferior parietal lobule -> crucial for visuospacial tasks
• here typically strength compared to females

Females:

• IFG, DLPFC -> Language, Regulation of sensation-seeking, risk-taking etc

1. moto cortical network - motor preparation and execution
2. right fronto-parietal network - attentional monitoring
3. left fronto-parietal network - response inhibition
4. middle cortico-subcortical network - error processing
5. cuneus-precuneus network - behavioral engagement
6. "default" network - self-referential processing

Wennde ufm moto farsch muesch links -> luege, git dr vortritt aso nume attention; rechts -> stop (inhibition), wöu de het är Vortritt. Um ke fähler (error processing) ds mache farsch ihr midline. Wenn nüt cunnt (Cuneus-präcuneus), de chasch im default witerfahre und uf di säuber luege

Significantly decreasing modularity:

-> there is reduced functional segregation in the brain

-> more regions are grouped together to achieve certain functions

There is reduced connectivity in default mode network in aged brains

Executive function:

1. working memory: Retain and manipulate info for short periods of time
2. mental flexibility: sustain or shift attention in response to difficult demands
3. self-control: set priorities & resist impulsive actions or responses

They develop relatively late, around the late schoolyears

Regulated by frontal temporal lobe and prefrontal cortex function

Inadequate development results in: 

- Hyperactivity, depression, poor attention, language difficulties

- inability to self-soothe and problems with impulse control

1. Slowness, indifference, apathy, lack of initative
2. disinhibition, lack of social constraint, hyperactivity, grandiose thinking, euphoria

• computations are increasignly efficient and require less support (base to grow on initially) and some processes switch
• efficiency: whatever causes there to be decreased activation -> itnerpreted as more efficient processing

= refers to brain regions playing more general roles in cognitive processing, rather than performing specific tasks

• an example is the fronto-parietal network:
  • maintenance of task sets or goals
  • direction of attention to particular stimulus features or dimensions
  • resolution of interference from competing sources of information
• in early development = support for early task performance
• later = gradually recedes as more specialized functions develop through learning and/or maturation

= a less mature process is abandoned for a more mature process -> reading development

= decorrelated activity between cortical neurons leads to a corresponding ecrease in connectivity between the decorrelated neurons and conversely so for correleated neurons

= constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory tasks

Leads to enhanced connectivity strength of certain brain regions due to coactivation. But the Default mode network (medial frontal and posterior cingulate cortex do not change). 

• epigenetic changes: can be due to life experiences and can have long-lasting effects, such as the regulation of Hypothalamus-pituitary-adrenal axis -> has influence on the regulation of the stress response
  • PTSD people have increased sensitivity to glucocorticoid receptor activation in the HPA feedback system --> Cortisol leads to an increased suppression of the HPA feedback system
• PTSD has been shown to be highly heritable
•  

Is associated with alterations in fear neurocircuitry:

• Bottom-up processes associated with the amygdalar response to threat = exaggerrated
• Top down: regulation of those processes by the prefrontal cotrex and hippocampus are impaired

Chronic stress has the same effect

Anticipation: avoid or reduce the impact of potential threat -> cognitive, affective and behavioral processeds

1. Mesolimbic pathway:

• bundle of dopaminergic fibres
• origin: Ventral tegmental area (VTA)
• projection: structures of the limbic system -> Nucleus accumbens
• Functions:
  • memory and motivating behaviours
• This pathway is blocked by antispsychotic drugs -> reduce intense emotions caused by conditions such as schizophrenia

2. Mesocortical pathway:

• origin: VTA
• projection: frontal cortex and surrounding structures
• malfunction: disordered thinking
• blocking: less psychotic deliriium, less overall activity of frontal lobes

3. nigrostriatal pathway:

• origin: substantia nigra
• projection: striatum -> motor control
• degeneration: trembling and muscular rigidity of Parkinson's disease

4. Tuberoinfundibular:

• connects the hypothalamus to the pituitary gland, where it influences the secretion of hormones

- affect the VTA and Nucleus Accumbens

- secondary: caudate nucleus -> stereotyped behaviours (nail biting and scratching)

- regular consumption -> leads to reduced metabolic activity in the frontal cortex, leading to multiple cognitive deficits

- these areas have high dopaminergic synapses -> preferred targest

- acton the VTA and Nucleus accumbens and other areas naturally mdoulated by endorphins(amygdala, locus coerucleus, arcuate nucleus, periaqueductal grey)

- also affect thalamus -> analgesic effect (pain killing)

- affect the basic rewards strucutres

- structures that use GABA as a NT -> major inhibitory neurotransmitter of the brain (Cortex, cerebellum, hippocampus and amygdala) 

-> Alcohol resembles exactly the structure of GABA and has the same effect on these brain structures. 

- THC -> concentrates in the VTA and Nucleus accumbens

- hippocampus -> memory proplems

- cerebellum -> loss of coordination and balance

- Locus coeruleus and its noradrenergic neurons -> movement and attention

- also the cholinergic neurons are affected

- Hippocampus and cortex -> increased vigilance and attentiveness

= Changes in the effectiveness of synaptic transmission

1. Habituation: activity dependent presynaptic depression of synaptic transmission -> e.g. you get used to a constant sound
2. Sensitization: presynaptic facilitation of synaptic transmission -> you hear a sudden, loud sound. Then you hear shit more clearly
3. Classical conditioning: Presynaptic facilitation which is dependent on activity in both the presynaptic and the postsynaptic cell

- involves the cAMP-PKA-MAPK-CREB Pathway and the synthesis of new proteins --> activate genes enxoding for proteins important in the formation of new synaptic connections

1. Perforant pathway
2. mossy fibre pathway
3. schaffer collateral pathway