Understanding the encoding of memory and its retrieval is a complex task. The neurobiological correlates of memory have been summarised in this presentation for easy understanding of students.

1. Neurobiology of
Memory
Dr Parth Goyal
Dr Priyal Desai

2. Important Definitions
• Learning: A process by which new information is acquired by the
nervous system and is observable through changes in behaviour
• Memory: Refers to the encoding, storage and retrieval of learned
information
• Synaptic Plasticity: The ability of the synapses to strengthen or
weaken over time.
• Strengthening of synapses over time is known as Long Term
Potentiation (LTP)
• Weakening of synapses over time is known as Long Term
Depression (LTD)

3. Neuro-Plasticity
• Synaptic connections between neurons provide
a basic wiring of the brains circuitry.
• This connectivity between neurons is dynamic
and is constantly changing in response to neural
activity and other influences.
• Synaptic Plasticity is of 2 forms: Short term and
Long term.

4. Long term Plasticity
• Two forms: LTP and LTD
• Long term Potentiation: It is a candidate for long
term memory function in mammalian brains.
• Occurs when a post synaptic neuron is
“Persistently Depolarised" after a “High
Frequency” burst from pre synaptic neuron.

5. Features of LTP
• Established quickly and lasts for a long time
(days to years)
• Associative in nature; occurs only at
“Potentiated synapses”, terminating at the post
synaptic cells
• Occurs prominently at the hippocampus;
structure that is pivotal to memory formation.

7. State of NMDA Receptors at Rest and while being
Depolarized

8. Mechanism of LTP
• http://sites.sinauer.com/neuroscience5e/animati
ons08.02.html

9. Long Term Depression
• If synapses would simply increase in strength due to
LTP, eventually it would be difficult to encode new
information
• Thus it is necessary to selectively weaken specific
set of synapses.
• LTD occurs when schaffer collaterals are stimulated
at 1 Hz for long periods.
• LTD can erase the increase in EPSP size due to LTP.

10. LTD In
Hippocampus

11. LTD in
Cerebellum

12. Types of Memory
• There are 2 main types of “Qualitative” memory
systems:
• a) Declarative: Storage and retrieval of material that
is available to the consciousness and can be
expressed in language.
• b) Non Declarative: Also k/a “Procedural Memory”,
something that is not available to the
consciousness. It involves “skills and associations”.

13. Categories of Memory

14. Temporal Memory Systems
• Memory can also be classified on the basis of
the “time” over which it is effective
• a) Immediate Memory
• b) Working Memory
• c) Long Term Memory

15. Temporal Categories of Memory

16. Memory Consolidation
• The way by which immediate and short term memories are
encoded into long term memories is known as memory
consolidation.
• Steps involved in memory consolidation:
• 1) The event is experienced and encoded by a virtue of the
cortical regions involved.
• 2) At the same time, the Hippocampus and the adjacent cortices
receive pertinent information
• 3) Later when the original event is recalled, the same set of
cortical regions get activated.

17. Contd..
• In case a subset of a cortical region is activated, the hippocampus and the
other structures can facilitate recall by activating the remaining cortical region.
This is known as “Pattern Completion”.
• If on retrieving the original event, it becomes associated with new information,
the Hippocampal-Cortical networks can be modified accordingly.
• In this way a gradual consolidation process occurs which can change the
nature of memory storage.
• The neo-cortical components over a period of time and on repeated recall can
become so efficiently linked, that the original event can be recalled without
any help from the hippocampus and the associated structures.
• Areas in the Frontal Lobe and the Temporal lobe are important in facilitating
this long term recall of information.

18. Techniques used in
Consolidation of Memory
• Some of the most commonly used methods are
• a) Priming
• b) Associative Learning
• C) Conditioned Learning.

19. Priming
• It is defined as: “ A change in the processing of a
stimulus due to a previous encounter with the same or a
related stimulus with or without conscious awareness of
the original encounter.
• However the information stored in priming is not
particularly reliable.
• Priming is resistant to brain injury, aging and dementia.
• Priming shows that previously presented information
always influences our subsequent behaviour.

20. Priming Test

21. Fallibility of Human Memory

22. Associative Learning
• Normal human capacity to remember a string of numbers is limited to
max 7-9 numbers.
• However some people are able to remember larger strings, by
employing other techniques that enhance memory.
• By “associating” the object in question with some meaningful form of
information, memory can be enhanced significantly.
• The capacity of memory depends very much on
• a) what the information means to the individual
• b) how it can be associated with the information already stored.
• Motivation also plays an important role in memory formations.

23. Role of Past experience, Context and Relevance in
Memory

24. Motivation in Memory

26. Conditioned Learning
• It is a category of non declarative memory that has been
most extensively studied in the past.
• It is defined as: “Generation of novel responses that is
gradually elicited by repeatedly pairing a novel stimulus
with a stimulus that normally elicits the response being
studied”
• Two main types:
• a) Classical Conditioning
• b) Operant conditioning

27. Conditioned Learning
• Conditioned Response
• Unconditioned Stimulus
• Conditioned Stimulus
• Unconditioned Response.

28. Operant Learning
• It refers to altered probability of a behavioural
response engendered by associating the
response with a reward or punishment.

29. Sleep and Memory
• Memory storage appears to be specifically
aided during deep sleep within a few hours after
learning (mostly prominent in stage 3 & 4, SWS)
• Some data indicates that the SWS facilitates the
storage of declarative memories and not non
declarative ones

30. Forgetting
• Initially it was believed that everything that is learnt is stored in the
brain, although sometimes particular details are not accessible.
• However this hypothesis has been proved wrong.
• People tend to gradually forget what they have stored in long term
memory, thus giving us more proof that our memory is unreliable at
best.
• Memories that are unused, unrehearsed and have not particular
importance deteriorate over time.
• Forgetting unimportant information is a crucial ability for leading a
normal life.

31. Brain systems involved in
storage of Declarative Memory
• Learning about the various structures of the brain involved
in storage of declarative memories is a challenge
• Much of the information is based on studies from individuals
who have sustained brain injuries.
• Taken together, these cases implicate the role of
• a) Midline diencephalic structures (Thalamus,
Hypothalamus)
• b) Medial temporal lobe structures (Hippocampus, Peri-
rhinal, Enterorhinal cortex and Para hippocampal region)

32. Contd..
• The studies discussed subsequently suggest
that primates and other mammals depend on
medial temporal structures, to encode and
consolidate memories of events and objects in
time and space,
• Just as humans use these same brain regions
for the initial encoding and consolidation of
declarative memories.

33. Contd.
• Studies (PET and fMRI) have shown that the neurons in the
hippocampus and para hippocampal cortex are selectively
recruited by tasks that involve declarative memory
formation.
• Studies have shown that the posterior hippocampus
appears to be particularly useful in remembering spatial
information. This is exhibited in the case of London Taxi
Drivers.
• Confirming the role of experience in performance the size of
the posterior hippocampus in cab drivers scales positively
with the number of months spent driving a cab.

34. Contd..
• Neuronal activation within the hippocampus and
the allied cortical areas of the medial temporal
lobe largely determine the “transfer of
declarative information into long term memory”
• and that the robustness with which such
memories are encoded, depends on structural
and functional changes, that occur as a result of
experience.

35. Structures involved in Storage of Declarative Memory

36. Role of Hippocampus in Memory

37. Long term Storage of
Declarative Memories
• We have seen that the immediate storage of
declarative memories occurs in the structures of
the medial temporal lobe
• However when these structures are damaged, due
to injury or illness, the patient “does not” forget the
memories that he acquired earlier in life
• This implicates the involvement of other regions of
the cortex in the long term storage of declarative
memories

38. Lines of Evidence
• There are multiple evidences that are available to
prove the following:
• a) Lashley’s “Mass action principle”, which states that
any degradation in learning and memory depends on
the amount of cortex destroyed; the more complex the
learning task the more disruptive the lesion should be.
• b) Patients undergoing ECT, usually show impairments
in retrograde memories ranging from a few hours to
days.

39. Contd..
• c) Patients with damage to the regions of
association cortex e.g the association cortex of the
inferior temporal lobe is involved in linking images
(faces/objects) with meanings. Damage to this
region affects the ability of the person to recognise
the objects, indicating that memory is also stored in
this region.
• d) Neuro-imaging Evidence: when subjects were
asked to recall words associated with images,
cortical areas got activated on recall.

40. Hippocampus and possible declarative memory storage
sites.

41. fMRI Studies to locate
memory sites.

42. Frontal Lobe and its
Contributions
• Role of Frontal Lobe: The association cortices
located particularly in the frontal lobe are
associated with retrieval of memories.
• The dorsolateral and anterolateral aspects of
Frontal lobe are activated when declarative
memories from long term storage are retrieved.
• Patients with damage to these areas fail to recall
these memories accurately and often resort to
confabulation.

43. Brain Systems involved in Non-Declarative
Memory acquisition and storage.
• Non declarative memories involve the:
• a) Basal Ganglia
• b) Prefrontal Cortex
• c) Amygdala
• d) Sensory association cortices
• e) Cerebellum
• They don’t involve the midline temporal lobe structures.

44. Lines of Evidence
• Ischemic damage to the cerebellum produces
profound deficits in classical eye-blink
conditioning but does not interfere with
formation of new declarative memories.
• Lesions in visual association cortex produce
profound impairment in visual priming but leave
declarative memory intact.

45. Contd..
• The basal ganglia and the prefrontal cortex are profoundly
important in non declarative memory recall.
• Evidence: Patients with huntington’s perform poorly on motor skill
learning tests, such as manually tracking a spot of light, tracing
curves using a mirror or reproducing the sequence of finger
movements.
• Patients with Parkinson’s as well as Prefrontal lesions caused by
strokes or tutors, show similar deficits on these tasks.
• Neuroimaging studies have corroborated these findings. Normal
individuals show activation of these brain regions while performing
these tasks.

46. Summary of Storage Sites

47. Disorders of Memory
• Memory disorders can be classified into 2 main
types:
• a) Physiological: Infantile Amnesia
• b) Pathological: Amnesia’s (Retrograde or
Anterograde)
• Amnesia’s most commonly occur due to brain
injuries, but some can also be Psychogenic in
origin.
47

48. Infantile Amnesia
• The absence of conscious memories fro the first 3 years of life is
known as Infantile Amnesia
• Traditional Views: Regression and Retrieval Failure.
• Present View: Declarative memories do not become fully available
by the age of 3 years, whereas non declarative emerges early in
infancy.
• Thus currently it is considered as a “failure of storage” rather than
failure of retrieval.
• The amnesia in this period is linked with the under development of
the neocortex, rather than that of the medial temporal structures.

49. Psychogenic Amnesia
• Memory problems arising due to psychological
factors is known as “psychogenic amnesia”
• It is important to differentiate psychological and
organic amnesia in a patient. Some of the points
of difference are:

50. Sr.
No
Features Psy Amnesia
Organic
Conditions
1 New Learning Capacity Intact Impaired
2 Retrograde Amnesia
Severe
(autobiograp
hical recall
impaired)
Autobiographical
memory is intact
3
Formal
Neuropsychological
Tests
Results variable
Results in sync
with the deficits
4 Course
Variable (Can
persist or can
resolve)
Usually persistent.

51. Psychological Amnesia V/S
Malingering
• Features in favour of genuine psychological
amnesia:
• 1) Tests scores are not as low as possible,
nerver worse than chance level
• 2) Memory access is improved by Amytal
Interviews
• 3) Significant premorbid psychiatric history.

52. Example of Psychogenic Amnesia

53. Retrograde and Anterograde
Amnesia’s.
• Inability to recall previously learned information
is known as Retrograde Amnesia
• Inability to learn new information across all
sensory modalities and stimulus domains is
known as Anterograde Amnesia
• Ribot’s Law: Deficits are most severe for
information that was most recently learned.

54. Case of H.M.
• Condition: intractable temporal lobe epilepsy. Got operated
for a bilateral temporal lobectomy.
• Structures removed: Hippocampus, Parahippocampus
corticies, Enterorhinal corticies, Piriform cortices, Amygdala.
• Pattern of memory deficits: Severe anterograde amnesia, with
impairments in explicit memory. b) Problems of committing
new events to his explicit memory c) impaired new semantic
knowledge d) moderate retrograde amnesia, upto 11 years
• Intact Domains: Intact working and procedural memory. b)
Intact motor learning skills c) Autobiographical memory recall

56. Case of K.C.
• Injury: Due to fall from motor cycle.
• Structure involved: Medial temporal lobe along with
complete B/L Hippocampus.
• Type of Amnesia: a) Severe anterograde with temporally
graded retrograde amnesia, which covers his whole life b)
Retrograde episodic memory c) Loss of emotional details
from past memories d) Loss of autonoetic consciousness
(unable to envision himself in the future)
• Intact Domains: Priming was intact. b) Semantic Memory
was intact

58. Case of N.A.
• Injury: Resulted from a mock duel from another service
man. Miniature fencing foil entered the right nostril and
then punctured the base of the brain.
• Structures involved: L-Thalamus, Posterior
Hypothalamus, Mamillary nuclei, Rt anterior temporal
lobe with amygldaloid complex.
• Patterns of amnesia: Severe anterograde amnesia for
declarative memory, more verbal than spatial. Fails
badly on formal tests of new learning ability. Deficits in
semantic memory seen.

59. Thank You