Q2 Schizophrenia

To what extent does the information presented in the article on (a) the general role of NMDA receptors and ...

Role of NDMA receptors

What does the book say?

(b) potential changes in brain oscillations and neurotransmitter function in schizophrenia correspond with the information presented in the course materials?(Hint: oscillations are mentioned in the course in the context of communications between neurons.)

Oscillations: Signal Theory

What does the book say?

How much are NMDA receptors and Oscillations linked?Evidence in Book? / Plausibility from knowledge of Book?

Books

What are oscillations?

Role in the singalling of elctrical synapsesbook 4 page 14

Were do electircal synapses exist

Role in the retina

Role in In hippocampus and Cortex

What do they do?

Book: What and where Elctrical Synapses produces Oscillations:"In the retina of the eye, for example, they are involved in the local integration of electrical activity between ensembles of retinal cells. Elsewhere in the brain they are involved in the generation of high-frequency electrical oscillations, similar to those seen during an epileptic seizure.

Distributed Memoryformation

If memory is ditributed, what belongs together has to be signalled somehow

If whole modules are distributed I.e. an emotional memory and the emotion itself the firing of thosestructures may need to besynchronized.

Cognitive processing

Book: Current Fuction is only Speculative: Current data suggest that the role of gap junctions is to facilitate instantaneous electrical rhythmicity in populations of neurons, if not whole brain structures. It has even been speculated that ultra-high frequency oscillations represent the ‘mind’ itselfBook: Whilst the function of these gap junction oscillations remains amystery, it has been proposed that in the cortex and hippocampus they may be implicated in cognitive processing, sensory perception and certain forms of distributed memory formation."

What is a NMDA Receptor?

Book 4 page 24Glutamate acts on many different types of receptor. One type, called the N-methyl-D-aspartate receptor (or NMDA receptor) is a neurotransmitter-gated ion channel that,unlike most other glutamate receptor-channels, is permeable to calcium ions. Inappropriate activation of this receptor induces toxic levels of intracellular calcium which canultimately lead to cell death (this toxic mechanism, termed excitotoxicity, is largely responsible for the brain damage induced by ischaemia and stroke)

Book 4 NMDA is a receptor in Hipporcampal Glutamatergic neurons=a Glutamate gated Ion channel

Book 4 Glutamate: The most widespread excitatory neurotransmitter in the brain but active i.e. in the hippocampus

Book 4 page 23:and aspartate excite virtually all neurons in the brain and spinal cord. Upon release from aglutamatergic terminal, glutamateis inactivated by reuptake intothe presynaptic and postsynaptic neurons

Book 5 page 35: NDMA receptor acts as a conincidence detector– it opens only when there is a conjunction of neurotransmitter in the synaptic cleft and a critical level of depolarization in the postsynaptic neuron, a temporal pairing of presynaptic and postsynaptic activation: a Hebbian synapse.

Book5: It is the influx of calcium ions into the postsynaptic cell, via the NMDA channel, that triggers the biochemical cascade that leads to the increase in synaptic efficiency

Book: The dual role of the NMDA receptor as an activity coincidencedetector and gateway for calcium entry during the induction of LTP

Book 4 Page24-NMDA receptor is malregulated it can be toxic

role memory andLearning

role several types learning

Book 38: especially spatial learning

Book Classical Conditioning

Book 39 role in the initiation of memory consolidation

Book 4 Initiation of Protein synthesis needed to maintain LTP

STM-->LTM

STM

Activation of NDMA-->STM

LTM

Strong Activation of NDMA-->LTM

Hebbian Learning

Modification of the synapse: Learing is increasing the efficiency of firing

By firing the post synaptic neuron is modified to work more efficient next time(more likely to fire)

Hebbian Synapse

A synapse that can be modiefied / made more efficient

In hebbian one neuron mightnot cause the other one to firebut be merely active at the same time

Where does one find NMDA receptors?

Book: Hippocampus

Role in Learning / LTP (Book 5 Chapter 1)

Book: Amygdala

Cole in fear conditioning

Article

NMDA

Where ...

Role in Interneurons

Generally in the brain

What ...

Disrupted Oscillations

Lacking or malfunctioningNMDA receptors as causal

Ocillations

What?

Disrupted patterns of oscllations seen in Schizophrenia

Where

not stated

hyothesis

Perhaps solution to major problem of communication: in brain if 2 neurons oscillate at the same speed the information belongs together

Book 1 Page 142 Binding Problem:there is no sinlge point where information flows togher: Where is shape colour category and sound of a car connected into one unified perception or awarness of a car

Perhaps those very fast electrical synapses syncronize other connected neurons with the help of those NDMA coincidence detectors.

Schizo vs. Epilepsy

Epilepsy caused by the synchronous firing of many neurons ending inSeizure

Drug work by decreasing efficacy of overactive sodium channel

Schizophrenia could be seen as a mild for of Epiliepsy

Perhaps missing sync in schizo causes 2 "I" s one of which is less dominant and only heard

However the missing sync is only oneof the problems in schizo - also problems in attention

Symptoms of sciciphrenia

Positive Symptoms

Hallucinations

Visual

Auditory

Negative Symtoms

Inabiltiy to focus attention

Inabilty of filtering out unimportant stuff

Cognitive Impairments

undordered thinking

Social Withdrawal