hippocampus Flashcards
1
Q
functional integration in the hippocampus
A
- mutlifunctionality
- multiple functions associated: rapid place and declarative learning, behavioural control including emotional motivational and sensorimotor functions
- integration of these functions may be a key feature of the hippocampus
- possibly an evolutionary purpose to this
2
Q
selective memory deficits in patients with hippocampal lesions
A
- patient HM: hippocampal damge following temporal-lobe reaction
- anorexia-induced hippocampal damage: during birth when problem with oxygen sypply, specific memory deficits
- patients with selective & extensive hippocampal damage show marked deficits in declarative memory, place and contextual memory
- other types of mem and general intellect are largely intact
3
Q
place learning deficits in rats with hippocampal lesions
A
- watermaze: learn how to get a platform, use spatial information
- hippocampal lesions: hippocampus specifically required for this type of learning, specifically damage neurons in the area that you want to study
- how long to get back to correct location: intact rapidly improve, cortical lesions do fine, hippocampal lesions struggle
- another way to measure through probe trials: search preferences, control show strong preference crossing target region, hippocampal lesions have absence of search preference
4
Q
rapid vs incremental learning
A
- rats with hippocampal lesions can very slowly acquire good place memory in the water maze
- HM can incrementally acquire accurate place memory
- complementary learning systems theory
5
Q
complementary learning systems theory
A
- hippocampus mediates rapid learning of place and declarative information, while extra-hippocampal (neocortical) sites can mediate slow incremental learning of such information
- like this, the two goals of rapidly learning about specific experiences and of extracting generalities from routine experiences can be reconciled
6
Q
place cells in the rat hippocampus
hippocampal firing correlates of learning and memory
A
- implant with electrodes into hippocampus
- record neural activity (action potentials) while they move around in watermaze
- neurons within place cells in hippocampus fire if they are in a particular location
- shows why an animal can remember certain locations
7
Q
beyond places
hippocampal firing correlates of learning and memory
A
- neuronal firing in the rat hippocampus also codes for other types of event information stored in the animal’s memory
- trial-type specific firing on a spatial-alternation task:
- alternates where to find food
- animal remembers more than just location of food - location and what happened in the location
- rats are rewarded for alternating between left and right turns
- hippocampus firing codes for right or left-turn trials
- two groups of neurons in addition to place cells (left and right) - this can be interpreted as animal remembering where they came from or prospective memory
8
Q
place cells in human hippocampus
A
- testing in virtual environment - remember certain locations
- patient (temporal love resection) shows place-responsive hippocampal neuron activity
9
Q
neuroanatomical basis of hippocampal learning
cortico-hippocampal interaction
A
- through the parahippocampal region, especially the entorhinal cortex, highly processed and mutlimodal sensory information from the sensory association cortices converges in the hippocampus
- entorhinal cortex important funnel of sensory information into hippocampus
- region is closely interacting with all sorts of neorcortical sensory association areas, all sensory modalities
- integrated into memory representations
10
Q
hebb’s hypothesis (1948)
A
- long-lasting change in the strength of connections between neurons is the physiological basis of lasting memory
- synapses between neurons are strengthened when the neurons are active together: ‘neurons that fire together wire tigether’
- would help us to understand how certain items get associated in memory e.g. certain items representing spatial locations
11
Q
hippocampal long-term potentiation
A
- long-lasting strengthening of a large proportion of synaptic connections
- many synaptic pathways in hippocampus show LTP
- e.g. long-lasting strengthening in response to strong concurrent stimulation of a large proportion of the synaptic connections that make up the pathway
- input from entorhinal cortex with different termination sites
- NMDA-type of glutamate receptors are required for induction of LTP in most hippocampal pathways
12
Q
blockade of hippocampal LTP and of place learning by NMDA receptor antagonist AP5
A
- combination with watermaze
- when give strong concurrent information very rapidly (tetanus) then go back to slower, response is markedly enhanced in control animal - LTP
- blocked AP5 (it is a NMDA receptor) don’t have this blocking
- control animals - strong preference for location
- with blocking - looks similar to a hippocampal lesion, only blocked synaptic plasticity so it is important for this type of memory
13
Q
encoding and retrieval
A
- encoding: configuration of stim evokes neocortical activity pattern, which excites a hippocampal ensemble. cortico-hippocampal connections & connections between hippocampal neurons are strengthened through the induction of synaptic plasticity
- retrieval: original neocortical pattern is partly reactivated, by a part of the original stimulus configuration, and excites a part of the hippocampal pattern
14
Q
hypotheses about receptors and how we can test this
A
- hippocampal NMDA receptors, supporting induction of synaptic plasticity, are important for encoding, but not retrieval, of one-trial place memory
- hippocampal AMPA receptors, mediating fast synaptic transmission, are important for encoding and retrieval of one-trial place memory
- experimental test: measurement of one-trial place memory when hippocampal NMDA or AMPA receptors are reversibly blocked during encoding or retrieval by intra-hippocampal infusion of specific receptor antagonists (AP-5 or CNQX)
15
Q
one-trial place memory task in event arena
distinct contributions of hippocampal NMDA and AMPA receptors
A
- during encoding trial, animals have to search to find a location where they can dig for a treat
- can use spatial cues to remember this
- then following a variable retention delay, animal needs to return to location with some new foil locations
- digging measure indicated strong memory for the correct location which declined with increasing retention delay (animals forget with time)
16
Q
effects of hippocampal NMDA or AMPA receptor blockade on encoding and retrieval
distinct contributions of hippocampal NMDA and AMPA receptors
A
- infuse NMDA or AMPA receptor blockers into hippocampus
- control as CSF solution
- NMDA blocker before encoding - don’t form a memory so cant discriminate between correct or incorrect locations
- NMDA blocker before retrieval - no impairment (NMDA important for encoding but not retrieval - 1st hypothesis)
- AMPA blocked before retrieval - impairment
17
Q
distinct electrophysiological effects of AP5 and CNQX
A
- animals implanted with stimulating electrode then record responses to this
- CNQX, but not AP5, reduces synaptic baseline transmission
- AP5 blocks induction, but not expression or maintenance, of LTP
18
Q
hippocampal dysfunction in normal age-related and pathological memory decline
A
- both normal age-related memory decline and pathological memory decline in early stages of Alzheimer’s disease, and its precursor stage mild cognitive impairment (MCI), mainly involve deficits in rapid learning of place or episodic information
- both normal ageing and early precursor stages of AD are characterised by alterations affecting the entorhinal-hippocampal circuitry
19
Q
disorders in which hippocampal dysfunction has been implicated
A
- hypometabolism - alzheimer’s, vascular disease
- hypermatabolism - SZ, depression, PTSD
20
Q
decreased hippocampal volume in SZ
A
- some atrophy in hippocampus in SZ patients
- confirmed with structural MRI and post-mortem exams
- structure reduced
21
Q
hippocampal function in SZ
A
- hippocampal overactivity at rest and impaired hippocampal recriutment in memory task
- increased hippocampal activity during auditory hallucinations
- converging evidence from human post-mortem and genetic studies and from animal models suggests hippocampal overactivity at rest as key feature of SZ pathophysiology
22
Q
excitation/inhbition balance in SZ
A
- reflects reduced neuronal inhibition within hippocampus
- glutamate transmission leads to post-synaptic depolarisation, making the neuron more likely to fire
- also have inhibitory neurons that interact with neurons within same region by inhibiting their activity (using chloride ions) and less likely to fire
- reduced hippocampal GABAergic inhibition may cause hippocampal overactivity
23
Q
post mortem evidence for hippocampal GABA dysfunction in SZ
A
- reduced presynaptic markers of GABA neurons in hippocampus
- compensatory upregulation of post-synaptic GABA receptors
- find very consistently in brains with SZ
24
Q
how may hippocampal dysfunction contribute to other functional impairments characteristing SZ?
A
- delusions & hallucinations as pathological hippocampus-dependent mems: abnormal interaction between hippocampal and sensory association cortices may cause sensory hallucinations
- probably wrong - would need specific activation of specific neurons
25
translating hippocampal memory into behaviour
* rapid encoding and subsequent retrievel of place and declarative memory --> translation into appropriate behaviour
* visuospatial information --> behavioural control
* within hippocampus along latitudinal axis there is a functional anatomical differentiation (septal, intermediate, temporal)
* behaviour happens via functional links that hippocampus has to memory related functions
26
accuracy of place-related neuronal firing decliens from septal to temporal pole
| functional differentiation along the longitudinal axis of the hipp.
* find less place related firing in temporal compared to septal pole
* place cells have different properties
* study: find less place cells when you move from septal to temporal pole, precision of place cells higher in septal (more fine grained representation)
27
involvement in fear/anxiety and the modulation of sensorimotor processes declines from temporal to septal pole
| functional differentiation along the longitudinal axis os the hipp.
* studies combined lesions to different parts of the hippocampus or functional inactivation by infusing a functionally inactivating drug or stimulations
* manipulate (inactivate) ventral hippocampus this has stronger impact of fear behaviours than dorsal hippocampus
* NMDA stimulation of temporal-intermediate, but not septal, hippocampus drives locomotion
* when you stimulate ventral hippocampus with NMDA this increases locomotor activity
28
temporal to intermediate hippocampus drives nucleus accumbens and prefrontal cortex dopamine transmission
* meso-corticolimbic dopamine transmission is implicated in a wide range of behavioural functions, including emotional motivational executive and sensorimotor processes, and may provide a key gateway to behavioural control for the hippocampus
* the temporal to intermediate, but not septal, hippocampus has indirect anatomical links to the VTA and direct projections to dopaminergic terminals in the PFC and the NAC
* via these links, activity of the temporal to intermediate hippocampus stimulates dopamine transmission in the PFC and the NAC
29
microdialysis studies: increased NAC and PFC dopamine during hippocampal stimulation
* sticking probes into area of interest
* content of the extracellular space in the brain diffuse from the extracellular space into liquid and can then analyse it
* use this method to measure dopamine transmission
* when stimulate temporal hippocampus - marked increase of dopamine transmission
* septal hippocampus - dont find this
* temporal hippocampus can +vely modulate nucleus accumbens dopamine transmission
* PFC also shows positive modulation of dopamine transmission by the ventral hippocampus
30
predictions from functional anatomical model
* intermediate hippocampus, where substrates of rapid place learning and links to behavioural control converge, is critical for behaviour baseds on rapid place learning
* neither the septal nor temporal pole can sustain such behaviour, as both possess only one of the two complementary sets of functional connectivity
* septal pole, through its connectivity with entorhinal cortex, can mediate rapid place encoding
31
experimental strategy for functional anatomical model
* behavioural performance on a task requiring rapid, one-trial, place learning
* electrophysiological models of rapid encoding in the septal hippocamppus (LTP and place-related firing)
32
rapid (one-trial)-place-learning task in the watermaze
* rat has to find target location where it can escape water, through spatial cues
* learn novel location each day
* trial 2: navigation depends on place memory encoded very rapidly during T1
* conceptually important trial. occassionally run as probe trial, with platform coming up before 60s - can measure search preference
* short retention delay - memory is very strong, strong search preference
* declines over 24hrs
33
ibotenate lesions sparing hippocampal tissue at different levels along the septo-temporal axis
* ibotenate = neurotoxin
* injected into different parts of hippocampus
* bits shown in white = what is left intact
* intermediate, but not septal or temporal, hippocampus can sustain performance based on one-trial place learning
* intact group does very well - strong search preference
* intermediate spared, virtually fine
* septal and temporal spared - impaired
34
electrophysiological models of hippocampal information encoding
* plasticity at entorhinal-hippocampal synapses: healthy evoked field potentials in septal remanent, doesn’t reflect problem with plasticity
* rapid place encoding:
* firing rate of one particular neuron
* put into new environment = rapid remapping which is stable
* septal spared - place encoding/representation present. Can learn a place rapidly, problems when translating into behaviour
35
functional interactions relevant for the learning-behaviour translation
hippocampal-prefrontal/subcortical interactions
36
functional significance of hippocampal dysfunction in neuropsychiatric diseases
integrative model suggest new hypotheses on how hippocampal dysfunction --> sympom generation
37
hypotheses relating to functional implications of hippocampal overactivity
* generally, hippocampal overactivity, disrupting appropriately tuned hippocampal neuron firing, may impair performance on hippocamus-dependent memory tasks by interfering with accurate visuo-spatial encoding or the translation of such encoding into adaptive behaviour
* strong overactivity involving temporal to intermediate hippocampus may drive projections to PFC and subcortical sites, including dopaminergic inputs
38
how to examine how hippocampal overactivity relates to network alterations in cortical and subcortical circuits and to behavioural impairments
* combination of functional imaging and neuropsychological testing in patients
* combination of in vivo neurochemical, electrophysiological, functional imaging, and pharmacological approaches with behavioural and cognitive testing in a rat model of hippocampal overactivity
39
anterior hippocampus overactivity is associated with psychosis in humans
* study compared regional cerebral blood volume (rCBV) in patients with SZ, prodromal patients, and healthy control ppts and examined correlations with symptoms
* the temporal ventral hippocampus corresponds to the anterior hippocampus in primates
* rCBV in part of anterior hippocampus is increased in patients with SZ compared to healthy control ppts
* also is increased in prodromal ppts who progress to psychosis as compared to those who dont
* also correlates with delusional symptoms
40
hippocampal overactivity is associated with cognitive impairments in SZ
* replication of overactivity at rest
* negatively correlated with cognitive performance
* too much activity - causes aberrant drive to frontal striatal circuits and thereby might disrupt these attentional vigilance functions that depend on frontal striatal circuits
* no causation
41
hippocampal neural disinhibition causes aberrant neural firing, as well as attentional and memory impairments
* hippocampal neural disinhibition - rat model of overactivity, reduced GABAergic activity in SZ
* aberrant neural spiking and bursting - firing rate following disinhibition impacted, particularly bursting
* rapid place learning performance in watermaze - overactivity causing memory problems in SZ preference, marked impairment in terms of search preference
* attentional preference on 5-choice-serial-reaction-time test - disruption in attentional performance with overactivity
42
THE HIPPOCAMPUS IS A BRAIN REGION IN?
THE MEDIAL TEMPORAL LOBE
43
PATIENT HM HAS HAD LARGE PARTS OF HIS HIPPOCAMPUS REMOVED SURGICALLY ON BOTH SIDES OF THE BRAIN. FOLLOWING THIS SURGERY, HE SHOWED MARKED IMPAIRMENTS IN SOME ASPECTS OF MEMORY FUNCTION, WHILE OTHER MEMORY FUNCTIONS WERE SPARED. WHICH MEMORY FUNCTION(S) WERE LARGELY SPARED?
PROCEDURAL MEMORY
44
THE HIPPOCAMPUS IS LINKED TO THE SENSORY ASSOCIATION CORTICES BY WAY OF DIRECT NEUROANATOMICAL CONNECTIVITY WITH THE
ENTORHINAL CORTEX
45
HIPPOCAMPAL LONG-TERM POTENTIATION REFERS TO
A LONG-LASTING INCREASE IN SYNAPTIC STRENGTH WITHIN THE HIPPOCAMPUS
46
THE MAIN EXCITATORY NEUROTRANSMITTER IN THE MAMMALIAN BRAIN IS
GLUTAMATE
47
THE MAIN INHIBITORY NEUROTRANSMITTER IN THE ADULT MAMMALIAN BRAIN IN
GABA
48
NMDA RECEPTOR ACTIVATION WITHIN THE HIPPOCAMPUS IS REQUIRED FOR THE *WHAT* OF MOST TYPES OF HIPPOCAMPAL EXCITATORY LTP
INDUCTION
49
AMPA RECEPTOR ACTIVATION WITHIN THE HIPPOCAMPUS FOR THE *WHAT* OF MOST TYPES OF HIPPOCAMPAL EXCITATORY LTP
INDUCTION AND EXPRESSION
50
BLOCKING NMDA RECEPTORS WITHIN THE HIPPOCAMPUS DURING *WHAT* OF ONE-TRIAL PLACE MEMORY DISRUPTS BEHAVIOURAL PERFORMANCE BASED ON THIS MEMORY
LEARNING
51
BLOCKING AMPA RECEPTORS WITHIN THE HIPPOCAMPUS DURING *WHAT* OF ONE-TRIAL PLACE MEMORY IS EXPECTED TO DISRUPT BEHAVIOURAL PERFORMANCE BASED ON THIS MEMORY
LEARNING OF RETRIEVAL
52
A PLACE CELL IS
A NEURON IN THE HIPPOCAMPUS THAT FIRES IF AN ANIMAL IS IN A PARTICULAR PLACE, BUT SHOWS COMPARITIVELY LITTLE OF NO FIRING OUTSIDE THIS PLACE
53
THE DISCOVERY OF HIPPOCAMPAL PLACE CELLS
SUGGESTS A NEURONAL MECHANISMS OF PLACE REPRESENTATION WITHIN THE HIPPOCAMPUS
54
THE DISCOVERY THAT HIPPOCAMPAL LESIONS IMPAIR PLACE LEARNING SUPPORTS THAT
THE HIPPOCAMPUS IS REQUIRED FOR PLACE LEARNING
55
OVERALL, STRUCTURAL IMAGING STUDIES SUGGEST THAT HIPPOCAMPAL VOLUME IN PATIENTS WITH SZ, AS COMPARED TO HEALTHY CONTROL PPTS IS
REDUCED, ESPECIALLY IN LATER STAGES OF THE DISORDER
56
OVERALL, FUNCTIONAL IMAGING STUDIES SUGGEST THAT HIPPOCAMPAL ACTIVITY IN PATIENTS WITH SZ, AS COMPARED TO HEALTHY CONTROL PPTS, IS *WHAT* AT REST, WHILE HIPPOCAMPAL ACTIVATION IN RESPONSE TO HIPPOCAMPUS-DEPENDENT TASKS IS *WHAT*
INCREASED, DECREASED
57
IS THIS TRUE ABOUT THE SEPTAL HIPPOCAMPUS: THIS REGION IS ALSO OFTEN REFERRED TO AS DORSAL IN RODENTS
YES
58
IS THIS TRUE ABOUT THE SEPTAL HIPPOCAMPUS: THIS REGION CORRESPONDS TO THE POSTERIOR HIPPOCAMPUS IN HUMANS AND OTHER PRIMATES
YES
59
IS THIS TRUE ABOUT THE SEPTAL HIPPOCAMPUS: PLACE REPRESENTATIONS IN THIS PART OF THE HIPPOCAMPUS ARE MORE ACCURATE THAN IN THE TEMPORAL PART
YES
60
ARE PLACE REPRESENTATIONS IN THE TEMPORAL HIPPOCAMPUS MORE ACCURATE THAN IN THE SEPTAL PART
NO, THEY ARE LESS ACCURATE
61
WHERE DOES THE INTERMEDIATE HIPPOCAMPUS SIT IN RATS
BETWEEN THE SEPTAL AND TEMPORAL HIPPOCAMPUS
62
DESCRIBE WATERMAZE
A BEHAVIOURAL TESTING APPARATUS THAT IS WIDELY USED TO TEST SPATIAL LEARNING AND MEMORY IN RODENTS
63
NEURAL DISINHIBITION REFERS TO A REDUCTION OF
INHIBITORY NEUROTRANSMISSION MEDIATED BY GABA
64
HIPPOCAMPAL NEURAL DISINHIBITION IMPAIRES ATTENTIONAL PERFORMANCE ON THE 5CSRT TEST, WHEREAS HIPPOCAMPAL LESIONS DO ESSENTIALLY LEAVE ATTENTIONAL PERFORMANCE INTACT. THESE FINDINGS SUGGEST THAT HIPPOCAMPAL ACTIVITY
MODULATES SUCH ATTENTIONAL PERFORMANCE
