Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_123_библиотеки_им_акад_М_И_Перельмана
.pdf
CHAPTER 15 Learning to Remember 291
behavior and can be considered as the formation of a predictive relationship
between a behavior and an outcome. It can use either rewards (reinforcement) or
punishment, each of which may be linked to positive or negative consequences of
some behavior.
Conditioned behaviors may be lost through a process called extinction. Extinction
results from changing the conditions so that the CS no longer predicts CR or so
that the operant consequence associated with the previously conditioned behavior
no longer happens.
Learning motor sequences:
Procedural memory
Procedural memory is the acquisition of skill in performing action sequences and
habit behaviors. It can involve conscious awareness in the initial learning and
acquisition of the skill, but not in the performance. Procedural memory is enhanced
by practice, repeating an action sequence until the sequence can be well executed
without conscious awareness.
Some procedural skills don’t involve actual movement. One example is planning
chess moves. Each chess piece moves according to certain rules. When practiced
chess players learn the piece move sequences, they activate neural circuits in the
cerebellum that are similar to those used for motor learning. Skillful players can
imagine a sequence of moves using this learned neural circuitry without actually
putting their hands on a chess piece.
A hallmark of procedural memory is the lack of conscious awareness of the steps
that make up the overall action sequence. One model for procedural memories is
that of a causal chain, where completion of one phase of the action sequence
directly causes the beginning of the next phase, without voluntary intervention of
any kind. This knowledge has been referred to as knowing how versus conscious
types of memory that involve knowing what.
For procedural memory, the basal ganglia may encode which actions to select for
a particular motor skill. For procedural memory, in concert with the basal ganglia,
the cerebellum acts as a feed-forward controller that stores action sequences from
the current state to the next state without the necessity of sensory feedback. Sen-
sory feedback is used during the learning phase for setting up the action sequence
so that appropriate movements are made. Procedural memory involves synaptic
plasticity changes described in the section “Looking at synaptic plasticity in
implicit memory” later in this chapter.
https://t.me/med1917
292 PART 3 Understanding Perception and Cognition
Preparing for priming
In priming, exposure to one stimulus can inuence a response to a subsequent
stimulus without conscious guidance or intention. Subliminal advertising is a now
banned example of priming, though it wasn’t eective. Other examples of prim-
ing are eective. If we ask you to play a word-association game and give you the
word bank, you could come up with words related to bank either as it refers to riv-
ers or money. If before giving you the word, we showed you an image of a river,
but so quickly that you were unaware of it, your responses to the word bank would
be reliably biased toward river, not money, associations.
Priming involves long-term memory not because the eect of a subliminally
ashed image (the prime) reliably lasts for a lifetime, but because the eect of a
prime activates the long-term memory system, including your world knowledge
semantics. The proposed mechanism is the automatic spreading of activation
between concept modes in semantic memory. This semantic system is sometimes
referred to as the perceptual representation system.
Focusing on Declarative Memory
Declarative memory involves the conscious or intentional retrieval of factual infor-
mation, concepts, and experiences. It’s subdivided into semantic and episodic
memory. Semantic memory is for facts, words, and concepts. Endel Tulving rst
proposed the idea of episodic memory for events and experiences, including those
that are autobiographical. The hippocampus and nearby cortex in the medial tem-
poral lobe are required to form new declarative memories. Memories are then
transferred from the hippocampus to cortical brain circuits that can be accessed
by dierent cues.
In the rst stage of the multi-store model, information enters into the sensory
register store. Most sensory input that activates sensory receptors in the human
body doesn’t reach conscious awareness, and most of what reaches conscious
awareness isn’t stored permanently in the human brain. Here we cover the char-
acteristics of sensory memory.
Fleeting sensory memories
Sensory memory refers to the perception of a picture (vision), sound sequence
(hearing), touch, smell, or taste for a very brief time after the stimulus has stopped.
Visual sensory memory is called iconic memory and lasts less than a second. Audi-
tory (echoic) memory appears to last longer, on the order of 2 to up to 10 seconds.
Less is known about somatosensory (haptic), olfactory, and taste memories.
https://t.me/med1917
CHAPTER 15 Learning to Remember 293
Seeing iconic memory in action
An excellent illustration of iconic memory is the Helmholtz covert memory exper-
iment. An array of 25 or more letters is ashed and the observer is told immedi-
ately after the ash to recall as many letters as possible in one location (say, upper
right). After the observer directs their covert attention toward some portion of the
array, they can name about seven items before the iconic neural image (iconic
memory) has faded.
Examining short-term memory
The process of naming the letters in the Helmholtz experiment entails consider-
able processing: converting the visual image to discrete letter objects, identifying
the letters, and associating the letters with names, in what is called semantics.
When the observer focuses attention on the sensory input, such as those semanti-
cally identied letters, a representation of the sensory memory is moved to short-
term memory. Short-term memory requires attention, has a limited capacity, and
decays over the course of a minute or so.
Both the time course and content of short-term memory can be strengthened. If
the letter names are rehearsed by repeating them over and over, the information
can be remembered for as long as the rehearsal occurs, and in some cases can lead
to it being encoded in long-term memory.
Short-term memory has a limited capacity. The commonly cited capacity of seven
items has been superseded byfour plus or minus one items. Although a person can
remember only about four dierent letters, they can also remember four dierent
familiar words or four short proverb-like sayings.
The content of short-term memory can be increased by the process of chunking.
The four slots in short-term memory aren’t slots for memory items, but slots for
memory addresses, or what computer science calls pointers. The pointer points to
any sort of memory conguration that has an identity with learned, strongly self-
reinforcing single internal learned congurations, such as letters, words, or short
proverb-like sayings.
Using short-term memory:
Working memory
Humans can manipulate and use the information stored in short-term memory
for dierent purposes, such as decision making, reasoning, calculating, and prob-
lem solving. This is called working memory. Working memory consciously
https://t.me/med1917
294 PART 3 Understanding Perception and Cognition
maintains representations of goal-directed knowledge, often maintained by
rehearsal, and used for cognitive processes.
In 1974, Alan Baddeley and Graham Hitch published a model of working memory
that consists of subsystems and a central executive. The visuospatial sketchpad
subsystem processes and stores visual and spatial information. The phonological
loop subsystem processes and stores auditory and verbal information. The epi-
sodic buer was added to the model in 2000 as a subsystem for information
retrieved from long-term memory and that can link information across domains.
The central executive is the supervisory system that controls attention, the ow of
information to and from the subsystems, and cognitive functions.
Researchers think the central executive is a function of the prefrontal cortex, par-
ticularly the lateral prefrontal cortex. Working memory is proposed to involve
persistent reverberating intrinsic circuit activity in the prefrontal cortex. The
memory lasts for as long as activity within the circuit is maintained, even when
the stimulus has stopped. Signaling pathways that lead to modication of neuro-
transmitter receptors may also contribute to working memory.
Addressing long-term declarative
(explicit) memory
Sucient rehearsal in short-term memory or the importance of information in
working memory can promote the transfer to long term storage. Long-term
declarative memory is typically created by conscious eort and conscious retrieval.
But in some cases, long-term declarative memories can be formed as a result of
emotionally salient experiences even if the brain doesn’t explicitly rehearse them.
Long-term declarative memory is integral to your understanding of the world and
yourself, shaping your current perspective and guiding your interactions. Declar-
ative means you can talk about it in words, and you can explicitly store and retrieve
these memories. Human declarative long-term memory has two main forms:
»
Semantic memory: General world knowledge. Semantic memory is what you
go to school to learn. It includes facts about the world in all subjects, language
usage including word denitions, and grammar and concepts. You also have
semantic memory for things you learn just by living.
»
Episodic memory: Memories of specic events. Episodic memory contains
source knowledge— knowledge of the time and context associated with an
event that may also have a semantic and emotional component. Some
episodic memory involves your own actions and experiences and is called
autobiographical.
https://t.me/med1917
CHAPTER 15 Learning to Remember 295
Episodic memory is more complex than other memories because it’s neither
primarily association, nor is it generated by rehearsal. Instead, it involves a
reconstruction of the entire context in which an event took place. Episodic
memory is dependent on activity in the prefrontal cortex, particularly the
lateral prefrontal cortex that instantiates working memory.
Spatial memory may also be considered a type of declarative memory. It allows
you to build a cognitive map of the world, plan a route to a desired location, and
remember where an object is located or where an event occurred.
Long-term memory is characterized by having a very large capacity and can
involve lifelong storage and retrieval. Encoding involves biochemical and mor-
phological changes to synapses and neurons.
Examining Brain Regions and
Memory Mechanisms
A short-term memory can become a long-term memory through the process of
encoding. It’s the job of the hippocampus to encode declarative and spatial mem-
ories. The hippocampus then transmits the encoded information back to circuits
in the cerebral cortex for long-term storage. Here we explain how information is
transmitted into, out of, and within the hippocampus.
Associating context with results
in the hippocampus
Short-term memory typically involves initial activity in a sensory input system.
High-level processing that leads to semantic item identication generates activity
in the lateral prefrontal cortex. This brain area maintains an internal representa-
tion of the input after the stimulus has ended. The lateral prefrontal cortex also
maintains other aspects of the current context, such as your goals and what you
were doing prior to that moment.
Inputting to the hippocampus
A region adjacent to the hippocampus, called the entorhinal cortex, provides the
majority of direct inputs to the hippocampus. The entorhinal cortex receives
information from many cortical and subcortical areas about what’s going on in
the current situation. The hippocampus also receives direct inputs from the basal
forebrain and the brainstem.
https://t.me/med1917
296 PART 3 Understanding Perception and Cognition
Remembering an episode involves reconstructing the salient aspects of the event.
Memory involves storing the patterns of brain activity associated with the event
so that the event and its context can be reproduced. Both the direct sensory rep-
resentation of inputs and their internal representation in lateral prefrontal cortex
and the amygdala provide input information, via the entorhinal cortex, to the hip-
pocampus. The hippocampus then creates the records of the events.
Understanding the intrinsic
hippocampal circuit
The main input tract to the hippocampus is the perforant pathway, where neurons
in the entorhinal cortex project their axons to dentate granule neurons in the den-
tate gyrus. The dentate granule neurons project axons called mossy bers to CA3
pyramidal neurons. CA3 pyramidal neurons project axons called Shaer collaterals
to CA1 pyramidal neurons. The main output from the hippocampus is from CA1 to
the subiculum, which projects back to the entorhinal cortex, and with other out-
puts to prefrontal cortex, perirhinal cortex, and amygdala (see Figure15-2).
In the hippocampus, the granule and pyramidal neurons are glutamatergic neu-
rons, and the majority of the synapses are excitatory synapses on dendritic spines.
GABAergic inhibitory interneurons in the hippocampus regulate the output from
the excitatory neurons.
FIGURE15-2:
Inputs to and
outputs from the
hippocampus.
© John Wiley & Sons, Inc.
https://t.me/med1917
CHAPTER 15 Learning to Remember 297
Looking at memory through
changes in synapses
Synaptic plasticityis the modulation of synaptic strength, where synapses become
stronger or weaker over time. Synaptic plasticity has been documented in a variety
of learning-associated brain areas including the hippocampus, cerebral cortex,
cerebellum, amygdala, and striatum.
The synaptic plasticity and memory hypothesis asserts that activity-dependent
synaptic plasticity is induced at synapses during memory encoding. It’s necessary
and sucient for the encoding and storage of the type of memory mediated by the
brain area in which it’s observed.
Discovering synaptic plasticity: LTP
Timothy Bliss and Terje Lomo discovered synaptic plasticity in the rabbit hippo-
campus in the 1970s. They stimulated axons in the perforant path from the ento-
rhinal cortex to the dentate gyrus with electrodes and measured postsynaptic
response in dentate granule neurons (refer to Figure15-2). They observed that
following a short burst of high frequency tetanic stimulation (100 Hz) of the
axons, there was a large and long-lasting increase in the postsynaptic responses
of the dentate granule neurons. This is now called long-term potentiation (LTP).
This discovery was of particular interest because at that time studies such as those
with H.M. were highlighting the hippocampus in declarative memory. Today LTP
is typically studied in brain slices in the Schaer collaterals, from CA3 axons to
CA1 neurons. Electrical stimulation of CA3 axons induces them to re action
potentials, and an electrode records dendritic excitatory post synaptic potentials
from a population of CA1 dendrites.
LTP induction
CA3 neurons are glutamatergic neurons. Their synaptic targets, CA1 neurons, have
dendritic spines that contain AMPA and NMDA type glutamate receptors. AMPA
receptors require only glutamate binding to be activated. NMDA receptors require
both depolarization (to remove the magnesium block) and glutamate binding to
be activated.
Following high frequency (tetanic) stimulation, glutamate is released by the CA3
axons, AMPA receptors are immediately activated, and the inux of sodium pro-
duces depolarization of the postsynaptic membrane called an EPSP.This depolar-
ization and the presence of glutamate activates the NMDA receptor channels,
mediating sodium and calcium inux, with a further depolarization and increase
in postsynaptic calcium levels.
https://t.me/med1917
298 PART 3 Understanding Perception and Cognition
Early phase of LTP
The increased calcium leads to the activation of protein kinases that phosphorylate
many substrates. The kinases include CaMK, PKC, PKA, and Erk. In LTP, the impor-
tant substrates are AMPA receptors and proteins involved in the tracking and teth-
ering of AMPA receptors. The phosphorylation results in an increase in the number
and activity of AMPA receptors at the post-synaptic membrane, and subsequently, a
larger synaptic response. The postsynaptic eect can be accompanied by changes in
the presynaptic CA1 axons that increase the amount of glutamate released.
The opposite of LTP is called long-term depression (LTD). It can be induced by stim-
ulating CA3 axons with a low frequency (1 Hz) stimulation. This too leads to CA1
AMPA receptor activation, but only a modest depolarization, partial activation of
NMDA receptors, and modest increase in intracellular calcium. This lower level of
calcium preferentially activates protein phosphatases that dephosphorylate AMPA
receptors and their tracking and tethering proteins. This results is a decrease in
the number and activity of AMPA receptors at the synapse and LTD.
In early LTP, the calcium and kinase activations occur within the rst 30 minutes
following electrical stimulation, but the eects persist in slices for many hours. In
addition to increased synaptic AMPA receptors, LTP involves biochemical and
structural changes to dendrites and synapses that maintain the potentiation. The
increase in calcium and activation of kinases in early LTP also lead to eects on
gene expression in late LTP.
Late phase of LTP
Late LTP involves regulation of transcription and translation that produce lasting
alterations of synaptic proteins and synaptic remodeling. In late LTP, changes in
transcription factors and dynamic epigenetic modications regulate gene expres-
sion and the levels of proteins involved in synaptic plasticity. Plasticity proteins
include additional transcription factors, AMPA receptors, scaolding proteins,
and brain-derived neurotrophic factor (BDNF).
Protein synthesis and cytoskeletal changes can lead to increased dendritic spine
volume and synaptic size.In some neurons, in late LTP, new synapses can also
form. LTD is accompanied by its own changes in gene expression and decreases in
dendritic and synaptic size.
Identifying additional mechanisms
in synaptic plasticity
Synaptic modications can depend on both presynaptic and postsynaptic
mechanisms. When synapses are simultaneously activated on a postsynaptic CA1
neuron, increasing calcium through NMDA channels, the CA1 neuron may
https://t.me/med1917
CHAPTER 15 Learning to Remember 299
synthesize and send a retrograde messenger back to the CA3 presynaptic axon.
This messenger can regulate neurotransmitter release and other activities.
Several retrograde messenger candidates have been identied. They include the
gaseous transmitters nitric oxide and carbon monoxide, and lipid mediators
including endocannabinoids. The neurotrophic factor BDNF, released from post-
synaptic CA1 neurons, has also been implicated as a retrograde messenger.
Evidence suggests that learning in healthy brains may also be accompanied by
neurogenesis, the formation of new neurons in the hippocampus. Neurogenesis
occurs in the dentate gyrus where new granule neurons are produced from pro-
genitors and has been proposed to be involved in hippocampal dependent memory
processes.
Physiological LTP
In the LTP tetanus experiment, strong electrical stimulation of CA3 axons pro-
vides robust presynaptic glutamate release that produces a very large depolariza-
tion of the postsynaptic spines. Under physiological conditions, these input
pathways never involve such high frequency stimulations.
Instead, the postsynaptic CA1 dendrites would normally receive many simultane-
ous small synaptic inputs from CA3 neurons, downstream of inputs from the
entorhinal cortex. In vivo, CA1 dendritic synapses will be potentiated if and only if
their inputs are simultaneously activated by coincident inputs. This is because
NMDA receptors require coincident membrane depolarization and glutamate
release by CA3 neurons.
The corollary is also true. When the presynaptic axon is active and, at the same
time, the postsynaptic neuron is only weakly activated by that or other inputs,
then the synapse formed by the presynaptic axon is weakened in LTD.
Sleeping for better long-term memory
Systems consolidation involves the process in which memories encoded by the
hippocampus are moved to neocortical circuits for permanent storage. Systems
consolidation is a slow dynamic process that may take weeks to months in humans.
It may involve circuit-wide changes in which all the neurons or all their synapses
undergo some type of similar biochemical change that coordinates and stabilizes
their activity as a neural circuit.
Long-term memory formation is a major function of sleep. Sleep provides an ideal
state for systems consolidation. During sleep, very little neuronal activity is trans-
mitted to the hippocampus or neocortex and stored memories are not accessed for
working memory. This reduces potential interference from activities that could
disrupt the processes of memory consolidation.
https://t.me/med1917
300 PART 3 Understanding Perception and Cognition
Both slow wave sleep (SWS) and rapid eye movement (REM) sleep are important for
consolidating declarative memory. One hypothesis is that systems consolidation
occurs during SWS during which the memory is transmitted from the hippocam-
pus to the circuits in the neocortex. Next, reorganization within the neocortical
circuits occurs during REM sleep.
Memories can be reactivated either during training of a task or during sleep after
the task. Studies show that replay during sleep may be important for systems con-
solidation. Though the mechanisms haven’t been identied, systems consolida-
tion may involve modication of cortical synapses through LTP-like mechanisms,
such that the cortex itself can reproduce the neural activity associated with an
experience.
The hippocampus participates in memory formation because hippocampal
neurons— whose synapses have been activated and strengthened by simultane-
ous inputs from the entorhinal cortex — project reciprocally back to the same
areas of the cortex. Long-term memory is thought to be stored in the same
cortical areas that represented the experience initially. The hippocampus is a
scratchpad for linking a set of neurons that were active during an event to form
the long-term memory of that event.
Resetting the hippocampus for future use
After a memory has been transmitted to the cortical circuit, the hippocampal syn-
apses that had been potentiated need to be reset. This ensures that the hippocam-
pus can be reused for future memory encoding. LTD may function in resetting the
potentiated synapses and also prevent saturation of synaptic activity. Resetting
may occur during sleep when the activity in the dendritic spines and excitatory
synapses is reduced
Needing the hippocampus for some
memory retrieval
Multiple trace theory contends that while semantic or context-free memories
become independent of the hippocampus over time, some episodic and contextu-
ally rich memories may always depend on the hippocampus. The theory asserts
that some memories are stored jointly in hippocampal and cortical circuits.
Another possibility is that the retrieval of stored contextually rich episodic mem-
ory could require the hippocampus to bind or synchronize its components.
Forming a cognitive map: Spatial memory
The hippocampus and entorhinal cortex are required for encoding spatial memo-
ries. Spatial memory allows you to form a cognitive map, responsible for
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана