• Sensory stimulus leads to short term memory (aka working memory) requires refreshing to use; later consolidates into long term memory refreshing not required
• Karl Lashley (1915) tried to localize memory by obliterating portions of cortex in rats and measuring their ability to learn a maze.
• The only correlation was between % of cortex gone and # of errors made.
• He concluded memory was not localized in specific memory traces (engrams) but distributed over a large area of cortex.

• Declarative memory (aka explicit memory): the capacity to consciously recollect facts and events.
• end product of this form of memory is the formation of memories. (i.e. memory of the first time you road a bike)
• Procedural memory (implicit memory): non-conscious abilities including skill learning, habits and forms of classical conditioning.
• end product is a change in behavior (i.e. being able to ride a bike)
• Memory Types have Distinct Neural Circuits
• Declarative memory: depends on cortico-limbo-diencephalic circuit: Hippocampus, Perirhinal cortex, Mamillary Bodies, Medial Dorsal and Ant. Thalamus, Neocortex; loop includes temporal lobe cortex and amygdala
• Patient H. M. illustrated the anatomical pathways involved in this type of memory following epileptic brain surgery
• Surgery = bilateral excision of temporal lobe structures: amygdala, parahippocampal gyrus, ant. 2/3 of hippocampus.
• H. M. experienced Anterograde amnesia = inability to remember events subsequent to onset of symptoms.
• H. M. did not experience Retrograde amnesia = inability to remember events prior to onset of symptoms.
• H. M.’s surgery interfered with declarative memory: ability to store and retrieve new memories (#s,faces,places,etc.)
• This type of memory is usually acquired in no more than one trial but can be forgotten rapidly.
• In other words he can form a working memory but cannot consolidate it into a long term declarative memory.
• Procedural memory: circuit is not fully understood but likely depends on cortico-striatal circuit:
• this loop includes the temporal lobe cortex, tail of the caudate nucleus, putamen, and cerebellum.
• concerned with the automatic acquisition of information like engaging in sports or playing an instrument.
• This type of information is acquired by repetitive trials.
• H. M. had no problem with this type of memory; he learned perceptual and motor skills at a normal rate.

Animal studies to confirm circuits – based on delayed respons tasks that rely on prefrontal cortex

• Lesions similar to those made in H. M. were made in monkeys, then were tested to assess function of memory types.
• Delayed nonmatching to sample (DNMS) tasks test Declarative memory.
• Experiment: animal is confronted with unfamiliar object, which it displaces to find a reward. After Ý delays, animal sees the same object paired with a new one. The task is to recognize original object and move to new one to obtain reward. Each pair is seen only once and correct choice is thus guided by the distinct memory of stimuli. (in monkey depends on prefrontal cortex and mediodorsal thalamus)
• cells in prefrontal cortex will light up during delay phase (working memory); cells don’t light up if animal forgets.
• Concurrent visual discrimination learning (DL) tasks test Procedural memory.
• Experiment: Animal is presented with 20 successive pairs of objects. within each pair, 1 object consistently conceals a reward. All 20 pairs are shown once a day until baited object is consistently chosen in each pair. Correct choice is guided by a "stimulus-response" connection.
• the results of these studies confirmed that lesions in the medial temporal lobe prevented performance of DNMS tasks when delay was > a few seconds and that DL task performance was unimpaired.
• similar studies of rats with hippocampal lesions have confirmed these results using mazes to show that hippocampus and perirhinal are most involved in remembering what is new and novel (Anterograde amnesia and DMNS)
• Hippocampus is also important to spatial memory: contains Place cells that create mental spatial maps that are not visually driven but are more a somatotrophic Cartesian 3D system.
• Place cells light up in "correlation" patterns that represent where rat thinks it is in space; the pattern seen when rats encounter a new environment seen during sleep that night. Rat is consolidating working memory by refreshing
• Fine lesions in Prefrontal Cortex show that cell groups store memory for specific classes of info (i.e all faces)
• additional studies have shown that damage to any area connected to medial temporal lobe also produces memory loss: medial dorsal nucl. of thalamus (highly reciprocally connected with prefrontal cortex); basal forebrain; mamillary bodies
• 80 % of Neocortex is association (most of temporal, parietal, frontal), presumably involved in memory formation

• Electroconvulsive shock therapy (ECT): treatment for depression that results in temporary anterograde amnesia and more permanent retrograde amnesia gradient where distant past is remembered better than period before treatment.
• Alzheimer’s disease (AD): irreversible memory loss likely due to degeneration in temporal lobe
• Korsakoff’s syndrome: antero-retrograde amnesia (EtOHÞ ß Vit B₁Þ damages dorsomedial thalamus/mamillary bodies/frontal cortex)
• Transient global amnesia: sudden onset antero and retrograde amnesia. Memory function recovers with some permanent loss. Etiology unknown. Linked to concussion, migraine, hypoglycemia and epilepsy; most likely TIA or embolism in PCA.
• Traumatic amnesia: proportional to severity of head injury. Retrograde amnesia mins prior; Anterograde 2-3 weeks.
• Infantile amnesia: non limbic (procedural) system matures before limbic memory system(declarative) Þ No baby memories
• Hebbian synapses: Coincidence = A/P in pre-synaptic cell causes A/P in post-synaptic cell. Repeated coincidence leads to an increase in the efficiency of conduction of A/P and larger post-synaptic response.
• Example: NMDA post-synaptic Glu receptor: normally pore is blocked by Mg⁺⁺; Glu releaseÞ A/P that dislodges Mg⁺⁺ from NMDA pore and allows conduction through NMDA receptor. So this specialized Glu receptor only works with A/P
• NMDA is a coincidence detector that not only allows Na⁺/K⁺ flux but also Ca⁺⁺. Ca⁺⁺ is thought to cause long term changes that make A/P transmission more efficient and thus may be how memories are stored.
• Hebb was also one of the 1^st to talk about cell assemblies (groups of cells active together). Memories must be refreshed, which may involve driving activity around in a reverberating circuit. This is the case with olfaction.