Traces of memory in the brain - Acsády László - 2017.03.30.

Richard Semon (1859-1918): discovered an interesting features of engram
	In case of evolutional neurobiology: it was not agreed in his time that Darwin is right and Lamarck was not
	Postulates:
		1) Engram is a persistent alternation in the brain as a result of a specific event
		2) The content is linked only to the information precieved during encoding
		3) Major feature of engram is ecphory > makes possible to change behaviour of engram
		4) The engram is in dormant state between encoding and retrieval > it does nothing until it is needed
	Engram: enduring, latent modification
	Ecphory: awakens the engram
Plasticity and substrate of engram
	Synaptic level
		> Long-term potentiation (ability of synapses to change their strength)
		> LTP can induce nuclear modification to produce new proteins
		> LTP effects dendritic spines: they can get stabilized
		> Many cells is involved in storing memories, yet it still means minor percent of cells
Life cycle of the engram
	Interconnections changes in strength > encoding
	Consolidation allows the system to store the memory for a long time > it does not require to repeat the stimulus
	Consolidation brings the memory to dormant state
	Reactivation of network > retrieval
	Reconsolidation occurs spontaneously
		> With help of reconsolidation, doctors can help to cure post-trauma
Engram in case of fear memory
	1st room: Small room, electrical shock > freezes
	2st romm: convinient > does not freezes
	1st room: freezes even if it does not get electric shock
	What happens in the brain?
		1st image: in all of the structures neurons of memory are active
		They consolidates in home room
		They get reactivated in first room
Neuronal representation of engrams
	Place cells: they fire when animal is in the place what they code > they represent an engram
		> 10 different place cells > sequence of activation of place cells represents the movement of animal
		> The interesting thing is measuring the same cell during sleeping: cells fire exactly in the same order as they did during the day
			> Now it is absolutely clear that that process is necessary for consolidation
			> During sleep brain condense time > it is needed to force cells to fire together to strengthen synapses by LTP
			> In short: during sleeping memories consolidates, so they become long term memories
		> With that method postulates can be completed:
			1) persistent, linked to special event
			2) linked to percieved information
			...
Replay the engram during sleep and memory consolidation
	1) Engram reactivates spontaneously
	2) 
	3)
	4) Sensory stimuli may recall memory
Specificity of coding and recalling the engram in humans
	Epileptic patients get electrodes in their brain to localize the problematic areas
		They were not exposed to specific event, only videos were shown to them
		The question was whether is there any specificity of neurons during watching videos
		The result was that there is specificity and when they asked to pronounce what they see, the neurons fired right before they pronounced the words.
Labeling (drmant) engram cells
	Let's allow the neurons to express all markers, but  ...
	Transgenic mice
	tetracyclin response element (TRE) > when in is not active than there is no transcription of immediate early genes
	tetracyclin transactivator protein > activates TRE
Optogenetic activation and inactivation of labeled engram cells:
	Inhibiting engram cells blocks freezing
	Exciting engram cells triggers freezing 
	Conclusion: Engrams are truly in the brain and they can be controled by optogenetic methods
Memory inpairment of Henry Gustav Molaison bilateral tempral lobectomy (1953):
	He could not learn anything, cannot remember new events, however, he was able to navigate in his small room
	Retrograde amnesia: forgot everything that happened in the last 11 years
	We remained a nice person, his "inner word" had not changed
	He was able to learn to draw with mirror
	Intact - Perceptual Priming
		Free recall: What did you read? > complex, contexual learnin > hippocampal lesion makes it impossible
		Perceptual priming: What words comes to your mind? > there is no different with patients with normal hippocampus and hippocampal lesion > hippocampus is not needed for completion of that task
Motor memory (procedural, implicit memory)
	Many training and practice
	Rigid recall: can be recalled only in identical situation > also cannot be easily changed
	Motor learning can be easily distracted by learing a little bit similar thing 
	After injury, other part of the brain can replace the demaged region (pasticity)
Event memory (declarative, explicit memory)
	Requires single event
	Difficult to distract
	Can be recalled in various situations
	No recovery after damage
Fear and reward memory
	Signigicant events may be sufficient
	Recalled in identical situation (e.g. in the same place)
	Highly pronounced vegetative output (e.g. heart)
Motor memory circuit: frontal cortex, thalamus, basal ganglia/cerebellum > plastic synapses are involved
Event memory circuit: temporal cortex+hippocampus ...
Fear memory: amygdala (very pronounced output), autonom centers, thalamus, prefrontal cortex
How they look like in brain?
	MEMORY SYSTEMS - 1.
		Papez-circuit (mamillary body, anterior thalamus): in case of rabies (veszettség), it is destroyed
			limbic system: emotions > patients are super honest, super agressive and super sexual