Mammalian Memory Mechanisms

• How much fear is exhibited when placed in the same context (how much a mouse freezes)
• This is hippocampus dependent

• How much fear is exhibited when a stimulus paired with an unpleasant sensation is cued 
• This is amygdala dependent

• The principle of dynamic polarisation: Information travels in only one direction from one neuron to the next.
• Information is stored through the modification of these connections

• When an axon of cell A is near enough to excite a cell B and repeatedly and persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficacy, as one of the cells firing B, is increased.
• “Cells that fire together wire together, Cells that are out of synch fail to link”

• 1: Long term memory 
• 2: Non declarative (implicit) memory
• 3: Declarative (explicit) memory 
• 4: Procedural (skills and habits)
• 5: Priming
• 6: Simple classical conditioning 
• 7: Non associative learning 
• 8: Facts 
• 9: Events
• 10: Medial Temporal lobe & Diencephalon 
• 11: Striatum
• 12: Neocortex
• 13: Emotional responses 
• 14: Skeletal musculature
• 15: Amygdala
• 16: Cerebellum
• 17: Reflex pathways

• At start of trial, food is at end of all 8 arms. Rat must find all the food.
• Performance = number of errors rat makes (i.e. number of time rat goes back down an arm he's already been down)
• Amnesic rats make lots of mistakes.
• HIPPOCAMPAL LESIONS CAUSE MEMORY PROBLEMS

• Milky water in a pool so can't see underwater. Rats put in pool and swim around til they find a submerged platform, so they can get out of the pool.
• In normal rat, the time it took to find the platform decreased in every subsequent trial.
• HPC lesion rats took the same length of time in every trial, as they couldn't remember they had been in the maze before/couldn’t learn where platform was.

• Maze has a N, E, S and W arm.
• Rat is trained that food is always put in same arm, and always starts running from same arm (e.g. rat always starts in N arm, and always runs to the food in the W arm).
• BUT on 8th day of testing, food is placed in the same arm, but the rat is put in a DIFFERENT arm to start.
• If the rat has learned the place, it will still run straight to the food. If the rat has learned the response, it will go in same direction as it always does (and bc they are now starting from a different place, they will not find the food.)
• Rats were in 2 groups. Some were injected with saline (no effect) and some were injected with lidocaine (shuts down cell action).
• They were injected in the Caudate nucleus or the Hippocampus

• Caudate nucleus (saline): Most rats learned PLACE route.
• Caudate nucleus (lidocane): Most rats learned the PLACE route.
• HPC, (saline): Most rats learned the PLACE route.
• HPC, (lidocaine): Rats chose PLACE route or RESPONSE route at random: they couldn't remember what way to go. They had impaired memory.
• On day 16 they injected them again.
• NOW most rats took RESPONSE route. BUT caudate nucleus-lidocaine rats took PLACE route.
• This suggests that the hippocampus gives a representation of room, to guide animals in space.
• By day 16, rats don't use spatial cues anymore; they turn L/R on autopilot.
• Caudate nucleus seems to be source of the autopilot: when it's disrupted on day 16, rats take the PLACE route again. SO HPC = PLACE LEARNING, CAUDATE NUCLEUS = RESPONSE LEARNING

• The persistent strengthening of synapses based on recent patterns of activity
• If PATHWAY is stimulated repeatedly, LTP will occur. But if after that, stimulus is applied to another pathway with some of the same neurons, nothing happens.
• LTP is about repeated stimulation giving rise to a state where the post-synaptic neuron's potential increases (as in it's membrane potential) in response to the SAME pre-synaptic input.
• Might be more NT being released with each AP from pre-synaptic neuron. OR the number of NT receptors on the post-synaptic membrane may increase, or the magnitudes of secondary messengers

Neurons which often fire together will begin to sprout new dendritic branches and axon terminals to increase connectivity.

• Raphe nuclei 
• Locus coeruleus
• Ventral tegmental area
• Thalmus
• MMB
• Amygdala
• Medial septum

The ability of a neuron to sense the simultaneous occurrence of synaptic activity at different points on the same cell.

• Glutamate binding to NMDA receptor is ineffective because of Mg2+ block in channel
• Depolarisation of the cell by some other means (e.g. EPSP from nearby synapses) ejects Mg2+
• Now, glutamate binding will open ion channel and allow Ca2+ to enter the cell.

• Formation of more postsynaptic receptors (greater response)
• Increased release of neurotransmitter
• New terminal button sprouts 
• The neck of the dendritic postsynaptic spine becomes thinner, offering less electrical resistance, and faster action potential conduction

• Calcium entering through the NMDA (glutamate ion) receptor causes protein kinesis 
• This changes the effectiveness of postsynaptic AMPA receptors (mimics the effects of the neurotransmitter glutamate)
• Or generates a retrograde messenger that leads to a lasting increase in neurotransmitter release

• If synapses simply continued to increase in strength as a result of LTP, eventually they would reach some level of maximum efficacy, making it difficult to encode new information.
• Thus, to make synaptic strengthening useful, other processes must selectively weaken specific sets of synapses.
• Long-term depression (LTD) is such a process.
• Synaptic links become less efficient the less frequently they are used

• Investigated place cells 
• Each hippocampal place cell represents an area of the environment 
• Each cell typically responds in multiple places
• Different groups of cells are active in each place
• Groups say “you are here”, not individual cells
• Cells are stable over a longer period of time and provide a long-term memory for a given environment
• Place cells show ‘remapping’ when an environment changes substantially
• Monitored these cells as rats ran a maze 
• Watched the activation of these cells as the rats dreamt of running the maze