This is a preliminary review of new results on trace This is a - - PowerPoint PPT Presentation

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• Russian

Russian Conference Conference with with International International Participation Participation “ “HIPPOCAMPUS AND MEMORY: HIPPOCAMPUS AND MEMORY: NORM AND PATHOLOGY NORM AND PATHOLOGY” ” Pushchino Pushchino, , Russia Russia

July 25 July 25-

• 28, 2009

28, 2009

THE ROLE OF THE HIPPOCAMPUS IN TRACE CONDITIONING. THE ROLE OF THE HIPPOCAMPUS IN TRACE CONDITIONING.

Hegumen Theophan ( Hegumen Theophan (V.I.Kryukov V.I.Kryukov) )

• St. Daniel Monastery, Moscow
• St. Daniel Monastery, Moscow

This is a preliminary review of new results on trace This is a preliminary review of new results on trace conditioning that attempts to integrate them into conditioning that attempts to integrate them into the framework of the framework of Vinogradova Vinogradova’ ’s s (2001) Theta (2001) Theta-

• Regulated Attention Theory.

Regulated Attention Theory.

1

VINOGRADOVA VINOGRADOVA’ ’S S CA3 COMPARATOR HYPOTHESIS: CA3 COMPARATOR HYPOTHESIS: REPLY TO REPLY TO LISMAN LISMAN (2006) (2006)

1.

• 1. Lisman

Lisman (2006) states that (2006) states that “ “this hypothesis poses a difficulty; even this hypothesis poses a difficulty; even Vinogradova Vinogradova claims that septal responses are usually claims that septal responses are usually polymodal

• polymodal. If this is

. If this is correct then a CA3 comparator could not use septal information t correct then a CA3 comparator could not use septal information to decide

• decide

whether incoming information is novel or not whether incoming information is novel or not” ” (p.37). (p.37). 2.

• 2. Lisman

Lisman (1999) and (1999) and Lisman Lisman et al (2005) proposed an alternative hypothesis et al (2005) proposed an alternative hypothesis -

• that the comparator is in CA1, and not in CA3, because CA3 store

that the comparator is in CA1, and not in CA3, because CA3 stores s temporal/permanent memories, and sends them to CA1 along with di temporal/permanent memories, and sends them to CA1 along with direct rect sensory information from sensory information from entorhinal entorhinal cortex. cortex. 3.

• 3. Kryukov

Kryukov (2008) argues that (2008) argues that Vinogradova Vinogradova’ ’s s theory requires the CA3 theory requires the CA3 comparator neither to be modality specific, nor to be storing an comparator neither to be modality specific, nor to be storing any memory traces, y memory traces, but it allows for solving the novelty detection problem uniforml but it allows for solving the novelty detection problem uniformly, for all signal y, for all signal modalities, because novelty detection is an emerging property of modalities, because novelty detection is an emerging property of the whole PLL the whole PLL system, and not just a single part of it. system, and not just a single part of it. 4.

• 4. Vinogradova

Vinogradova’ ’s s theory backed by new data suggested new hypothesis to be theory backed by new data suggested new hypothesis to be proposed, that the hippocampus can function as a dual CA1 proposed, that the hippocampus can function as a dual CA1-

• CA3 comparator

CA3 comparator and thus resolving many difficult problems in classical conditio and thus resolving many difficult problems in classical conditioning. ning.

2

THETA THETA-

• REGULATED ATTENTION THEORY

REGULATED ATTENTION THEORY -

• BASIC

BASIC FEATURES FEATURES (Vinogradova, (Vinogradova, 2001) 2001)

• The t

The theta rhythm and the heta rhythm and the septo septo-

• hippocampal system play a key role

hippocampal system play a key role in the processes of selective perception, attention, and memory in the processes of selective perception, attention, and memory involving involving detection of novel and significant changes which should be detection of novel and significant changes which should be recorded in recorded in memory. memory.

• The CA1 field

The CA1 field-

• based information subsystem and the CA3 field

based information subsystem and the CA3 field-

• based

based regulatory subsystem jointly perform the functions of attention regulatory subsystem jointly perform the functions of attention and initial and initial recording of new memory traces. recording of new memory traces.

• The CA3 field compares the two main inputs to the hippocampus

The CA3 field compares the two main inputs to the hippocampus – – septal and cortical. Its output regulates the arousal and the t septal and cortical. Its output regulates the arousal and the theta heta-

• rhythm frequency, and monitors the information CA3

rhythm frequency, and monitors the information CA3-

• based subsystem.

based subsystem.

• The CA1 field

The CA1 field-

• based subsystem is circular or spiral delay line with

based subsystem is circular or spiral delay line with variable times of delay and simultaneously is the main hippocamp variable times of delay and simultaneously is the main hippocampal al

• utput to the related cortical and
• utput to the related cortical and subcortical

subcortical structures structures. .

3

THEORY OF THETA THEORY OF THETA-

• REGULATED ATTENTION: RADAR

REGULATED ATTENTION: RADAR ANALOGY ANALOGY (Vinogradova, 1975; Kryukov, 1991) (Vinogradova, 1975; Kryukov, 1991)

The main function of the hippocampus is to compare the new and e The main function of the hippocampus is to compare the new and existing xisting

• traces. Via the feedback system, a mismatch signal will regulate
• traces. Via the feedback system, a mismatch signal will regulate the frequency

the frequency

• f the theta rhythm, replaying the cortical traces and strengthe
• f the theta rhythm, replaying the cortical traces and strengthening them on

ning them on repetition. repetition.

4

DOMINANT ARCHITECTURE OF "NEUROLOCATOR" DOMINANT ARCHITECTURE OF "NEUROLOCATOR" (Kryukov et al, (Kryukov et al, 1990; 1990; Hegumen Theophan, Hegumen Theophan, 2004) 2004)

• The functional unit is a cortical oscillator (CO) composed of in

The functional unit is a cortical oscillator (CO) composed of integrate tegrate-

• and

and-

• fire neurons in a network

fire neurons in a network with local excitation links, recurrent with local excitation links, recurrent inhibition and non inhibition and non-

• specific inputs from

specific inputs from mRF mRF. .

• A

A septal septal oscillator (SO) serves as a coordinator

• scillator (SO) serves as a coordinator

( ("orchestra conductor "orchestra conductor“ “) for cortical ) for cortical oscillators during

• scillators during

information recording and replay. The two information recording and replay. The two-

• way link is

way link is non non-

• symmetrical, depending strongly on synchronization.

symmetrical, depending strongly on synchronization.

• Attention is switched from one CO group to

Attention is switched from one CO group to another either by way of another either by way of reset or through an automatic change of the reset or through an automatic change of the SO frequency by a signal SO frequency by a signal from the comparator output. from the comparator output.

• Information is recorded in an ensemble of locally linked cortica

Information is recorded in an ensemble of locally linked cortical l

• scillators whose lability is
• scillators whose lability is modified upon training in accordance with the

modified upon training in accordance with the phenomenon of the dominant phenomenon of the dominant rhythm assimilation. rhythm assimilation.

5

KEY ASSUMPTIONS OF "NEUROLOCATOR" KEY ASSUMPTIONS OF "NEUROLOCATOR" (Kryukov et al, (Kryukov et al, 1991) 1991)

• The model structure is similar to that of a standard phase

The model structure is similar to that of a standard phase-

• locked loop

locked loop (PLL), and at the same time, is arranged much like the regulator (PLL), and at the same time, is arranged much like the regulatory y subsystem of the limbic system, with the septum acting as the ce subsystem of the limbic system, with the septum acting as the central ntral pacemaker and the CA3 field being a comparator ( pacemaker and the CA3 field being a comparator (Vinogradova Vinogradova 1975, 1975, 2001 ). 2001 ).

• All COs serve as feature analyzers. They are inactive without s

All COs serve as feature analyzers. They are inactive without specific pecific inputs and fairly high arousal is essential for initiation of o inputs and fairly high arousal is essential for initiation of oscillations in the scillations in the Θ Θ/ /γ γ frequency range. frequency range.

• Attention is an emergent feature of the system, which appears w

Attention is an emergent feature of the system, which appears with an ith an increase of arousal and manifests itself as transient synchroniz increase of arousal and manifests itself as transient synchronization of SO ation of SO with a certain group of COs. with a certain group of COs.

• Learning and consolidation rely on

Learning and consolidation rely on space space-

• frequency plasticity

frequency plasticity, involving , involving gradual changes in the natural frequency of COs towards the sync gradual changes in the natural frequency of COs towards the sync frequency in the learning process. frequency in the learning process.

6

SPACE SPACE-

• FREQUENCY SPATIAL PLASTICITY OF RECEPTIVE

FREQUENCY SPATIAL PLASTICITY OF RECEPTIVE FIELDS (RF) IN THE AUDITORY CORTEX OF A RAT FIELDS (RF) IN THE AUDITORY CORTEX OF A RAT (Weinberger, (Weinberger, 2003) 2003)

" "RF plasticity has major characteristics of associative memory. I RF plasticity has major characteristics of associative memory. It is not only t is not only associative, but also it is highly specific, discriminative, rap associative, but also it is highly specific, discriminative, rapidly acquired, idly acquired, retained at least for many weeks, develops consolidation over ho retained at least for many weeks, develops consolidation over hours and days, urs and days, and exhibits generality across a variety of training tasks". (We and exhibits generality across a variety of training tasks". (Weinberger, inberger, 2003, 2003, p. p. 271) 271)

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THE BLOCK DIAGRAM AND BASIC EQUATION OF THE BLOCK DIAGRAM AND BASIC EQUATION OF "NEUROLOCATOR" "NEUROLOCATOR" (Kryukov, (Kryukov, 1991) 1991)

where where ϕ ϕ

i i —

— difference between oscillation phases of the septal and the difference between oscillation phases of the septal and the i i-

• th

th cortical cortical

• scillators;
• scillators; Λ

Λ

0i 0i —

— their frequency mismatch; their frequency mismatch; A Aoj

• j —

— activity of neocortical oscillators activity of neocortical oscillators corresponding to the corresponding to the j j-

• th

th lamella; lamella; g( g(τ τ) ) — — nonlinear function of phase discriminator; nonlinear function of phase discriminator; N Nj

j (t

(t) ) — — "white" noise of the "white" noise of the j j-

• th

th lamella; lamella; n n — — total number of lamellas; total number of lamellas; F(p F(p) ) — — transfer function of the low transfer function of the low-

• pass filter

pass filter mRF mRF. .

8

ATTENTION ATTENTION-

• RELATED FEATURES OF "

RELATED FEATURES OF "NEUROLOCATOR NEUROLOCATOR" "

• Attention is transient. It is impossible with either too low or

Attention is transient. It is impossible with either too low or too high too high arousal. arousal.

• Attention is controlled by changes in the frequency

Attention is controlled by changes in the frequency detuning detuning ( (Λ Λ0

0 )

) produced either automatically from the produced either automatically from the comparator output or volitionally from other brain comparator output or volitionally from other brain structures. structures.

• Attention is controlled automatically by codes of external

Attention is controlled automatically by codes of external signals at signals at the theta rhythm frequency (spatial features) as the theta rhythm frequency (spatial features) as well as at its own well as at its own harmonic frequencies (non harmonic frequencies (non-

• spatial

spatial features), if less efficiently. features), if less efficiently.

• Attention is normally unitary, but with a certain reduction in

Attention is normally unitary, but with a certain reduction in parameter parameter of arousal it may be divided among

• f arousal it may be divided among 4

4-

• 7

7 objects

• bjects.

.

9

MEMORY MEMORY-

• RELATED FEATURES OF "NEUROLOCATOR"

RELATED FEATURES OF "NEUROLOCATOR"

• Memory capacity is practically unlimited, as encoding by

Memory capacity is practically unlimited, as encoding by isolabile isolabile configurations (ensembles) allows the temporary recruiting of os configurations (ensembles) allows the temporary recruiting of oscillators cillators from other configurations. from other configurations.

• L

Lifetime of ifetime of metastable metastable memory traces is comparable with that of an memory traces is comparable with that of an

• rganism, given an optimal number of the locally linked oscillat
• rganism, given an optimal number of the locally linked oscillators.
• rs.
• Signals are quickly recorded owing to simultaneous reset excitat

Signals are quickly recorded owing to simultaneous reset excitation ion

• f all the oscillators encoding the stimulus
• f all the oscillators encoding the stimulus.

.

• Many

findings

• f

psychophysical, neuropsychological, and Many findings

• f

psychophysical, neuropsychological, and neurophysiological neurophysiological research on memory may be easily explained by the research on memory may be easily explained by the well well-

• know features of the PLL system.

know features of the PLL system.

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WHAT IS TRACE CONDITIONING? WHAT IS TRACE CONDITIONING? IT IS ONE OF THE FOUR BASIC CONDITIONING PARADIGMS, IT IS ONE OF THE FOUR BASIC CONDITIONING PARADIGMS,

AND THE MOST DIFFICULT TO MODEL MOST DIFFICULT TO MODEL

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WHY TRACE CONDITIONING IS IMPORTANT BUT DIFFICULT WHY TRACE CONDITIONING IS IMPORTANT BUT DIFFICULT TO MODEL ? TO MODEL ?

• Requires intact hippocampus,

Requires intact hippocampus, mPFC mPFC, cerebellum, NC and interaction , cerebellum, NC and interaction between them ( between them (Kalmbach Kalmbach et al, 2009). et al, 2009).

• Requires attention, awareness and

Requires attention, awareness and neurogenesis neurogenesis ( (Shors Shors, 2004). , 2004).

• Most simple example that can dissociate declarative memory from

Most simple example that can dissociate declarative memory from procedural one and provides means for studying awareness in anim procedural one and provides means for studying awareness in animals als Clark and Squire,1998) . Clark and Squire,1998) .

• Perhaps requires common neural code for cognition and action.

Perhaps requires common neural code for cognition and action.

• Demonstrate full power of Theta

Demonstrate full power of Theta-

• Regulated Attention Theory by

Regulated Attention Theory by Vinogradova Vinogradova (2001). (2001).

• In general:

In general: “ “Trace Trace eyeblink eyeblink conditioning conditioning may may prove prove to to be be the the Rosetta Rosetta stone for identifying neuronal/synaptic mechanisms underlying de stone for identifying neuronal/synaptic mechanisms underlying declarative clarative memory formation i memory formation in n the brain the brain” ” (Christian and (Christian and Thompson Thompson, 2003). , 2003).

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BASIC UNANSWERED QUESTIONS BASIC UNANSWERED QUESTIONS

1.

• 1. “

“What What does does the the hippocampus hippocampus do do during during trace conditioning trace conditioning? ?” ” ( (Shors Shors, 2004, , 2004, p.252) p.252) 2.

• 2. “

“How does the hippocampus How does the hippocampus ‘ ‘know know’ ’ what information must be processed and what information must be processed and maintained for establishing a hippocampus maintained for establishing a hippocampus-

• dependent trace memory versus that

dependent trace memory versus that for the delay for the delay-

• type memory?

type memory?” ” ( (Shors Shors, 2004, p.252) , 2004, p.252) 3.

• 3. “

“A A major unanswered major unanswered question question concerns the concerns the relation relation between the between the cerebellum cerebellum and and hippocampus in eyeblink conditioning hippocampus in eyeblink conditioning” ” ( (Christian Christian and and Thompson Thompson, 2003, , 2003, p.4) p.4). .“ “How How are are the the cerebellar cerebellar, , hippocampal hippocampal, , and and cortical cortical systems functionally systems functionally interconnected interconnected? ?” ” ( p.11) ( p.11) 4.

• 4. “

“How awareness influence this form How awareness influence this form of learning, and the nature of

• f learning, and the nature of

hippocampal hippocampal involvement in such an involvement in such an interaction? This is interaction? This is a a most most interesting and interesting and important important current area of current area of research research “ “( (Christian Christian and and Thompson Thompson, 2003, p.6) , 2003, p.6). . 5.

• 5. “

“Where is the trace in trace conditioning Where is the trace in trace conditioning? ?” ” ( (Woodruff Woodruff-

• Pak

Pak and and Disterhoft Disterhoft, , 2008, p.105) In the hippocampus, 2008, p.105) In the hippocampus, cerebellar cerebellar, PFC, or in the neocortex ? , PFC, or in the neocortex ?

13

HIGHLY SIMPLIFIED SCHEMATIC DRAWING OF THE TRACE HIGHLY SIMPLIFIED SCHEMATIC DRAWING OF THE TRACE EBC EBC

(Green and Woodruff (Green and Woodruff-

• Pak, 2000)

Pak, 2000)

14

PROPOSED MODIFICATION BASED ON NEW DATA PROPOSED MODIFICATION BASED ON NEW DATA

CA1 CA1

15

CA3 CA3 Takacs et al, 2008

Kalmbach et al, 2009 Vinogradova, 2001 Vinogradova, 2001

THEORY OF THETA THEORY OF THETA-

• REGULATED ATTENTION: RADAR

REGULATED ATTENTION: RADAR ANALOGY ANALOGY (Vinogradova, 1975; Kryukov, 1991) (Vinogradova, 1975; Kryukov, 1991)

The main function of the hippocampus is to compare the new and e The main function of the hippocampus is to compare the new and existing xisting

• traces. Via the feedback system, a mismatch signal will regulate
• traces. Via the feedback system, a mismatch signal will regulate the frequency

the frequency

• f the theta rhythm, replaying the cortical traces and strengthe
• f the theta rhythm, replaying the cortical traces and strengthening them on

ning them on repetition. repetition.

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THE LAW OF YERKES THE LAW OF YERKES – – DODSON AND TRACE/DELAY DODSON AND TRACE/DELAY DISSOCIATION DISSOCIATION

1.

• 1. The quality of any task performance varies as inverse U

The quality of any task performance varies as inverse U-

• shaped function of arousal.

shaped function of arousal. 2.

• 2. The optimal arousal, corresponding to the best performance, is r

The optimal arousal, corresponding to the best performance, is relatively low for elatively low for complex tasks. complex tasks. 3.

• 3. Given increased arousal, attention is focused on the main aspect

Given increased arousal, attention is focused on the main aspect of the situation at the

• f the situation at the

sacrifice of other aspects, and the curve width is reduced. sacrifice of other aspects, and the curve width is reduced.

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"NEUROLOCATOR" EXPLAINS TWO DOUBLE "NEUROLOCATOR" EXPLAINS TWO DOUBLE DISSOCIATIONS DISSOCIATIONS

It is impossible to draw a clear line of demarcation between tra It is impossible to draw a clear line of demarcation between trace and delay conditioning, ce and delay conditioning, but there is a basic difference between declarative and non but there is a basic difference between declarative and non-

• declarative memory.

declarative memory.

Л AK

Λ AK

Trace Delay

max g 1 min g 1

< <

) Kg( A Λ dt d ϕ ϕ ϕ − =

Λ AK

(1) (1) (2) (2) (3) (3)

18

t US t CS t US t CS A ϕ ϕ − + + =

Λ AK

THE MAIN TRACE CR EFFECTS ARE EXPLAINED BY THE MAIN TRACE CR EFFECTS ARE EXPLAINED BY THE THE “ “NEUROLOCATOR NEUROLOCATOR” ” MODEL MODEL

• Intact

Intact septo septo-

• hippocampal system,

hippocampal system, mPFC mPFC, NC, cerebellum are critical for trace , NC, cerebellum are critical for trace CR ( CR (Kalmbach Kalmbach et al, 2009) . et al, 2009) .

• There exists an o

There exists an optimal set of stimulus timing and intensity parameters for ptimal set of stimulus timing and intensity parameters for trace conditioning that makes it a difficult task in a non trace conditioning that makes it a difficult task in a non-

• optimal regime.
• ptimal regime.
• Attention (Han et al,2003) and awareness (Clark and Squire, 1998

Attention (Han et al,2003) and awareness (Clark and Squire, 1998; ; Weike Weike et al et al 2007; Knight et al, 2006) 2007; Knight et al, 2006) are required. are required.

• Theta is critically important for all basic trace effects, but e

Theta is critically important for all basic trace effects, but especially for the specially for the following following (a) (a) Neocortical gamma activity is coordinated by the hippocampal Neocortical gamma activity is coordinated by the hippocampal theta ( theta (Sirota Sirota et al, 2008) et al, 2008) (b) (b) Attention and awareness are theta Attention and awareness are theta-

• contingent (

contingent (Klimesch Klimesch et al, et al, 2001; 2001; Doesburg Doesburg et al, 2009) et al, 2009) (c) (c) Theta Theta-

• contingent learning is several times faster (Griffin et al,

contingent learning is several times faster (Griffin et al, 2004) 2004)

• Time intervals are learned before the expression of trace CR, n

Time intervals are learned before the expression of trace CR, not otherwise

• t otherwise

(Drew et al, 2005). (Drew et al, 2005).

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THE MAIN MODEL PREDICTIONS THE MAIN MODEL PREDICTIONS

• While the site of permanent storage of trace EBCR has not been

While the site of permanent storage of trace EBCR has not been determined as of yet (Woodruff determined as of yet (Woodruff-

• Pak and

Pak and Disterhoft Disterhoft, 2008), the model , 2008), the model predicts that the neocortex acts as a permanent repository of l predicts that the neocortex acts as a permanent repository of learned earned responses acquired by forebrain regions, with the hippocampus responses acquired by forebrain regions, with the hippocampus including. including.

• Despite the prevailing view that striatum serves as the

Despite the prevailing view that striatum serves as the ‘ ‘core timer core timer’ ’ ( (Meck Meck et al, 2008), the model predicts that medial septum serves as a et al, 2008), the model predicts that medial septum serves as a global pacemaker and (jointly with global pacemaker and (jointly with septo septo-

• hippocampal system) as a

hippocampal system) as a ‘ ‘core core timer timer’ ’ of variable speed and times.

• f variable speed and times.
• Depending on the kind of the task requirement, or paradigms, the

Depending on the kind of the task requirement, or paradigms, the hippocampus can function as theta phase comparator (CA3), or as hippocampus can function as theta phase comparator (CA3), or as a a time comparator (CA1), or both, acting on a common septal theta time comparator (CA1), or both, acting on a common septal theta

• scillator to change the frequency of the oscillations.
• scillator to change the frequency of the oscillations.
• Due to a circular, or spiral, mode of neural reverberation in a

Due to a circular, or spiral, mode of neural reverberation in a CA1 CA1 based subsystem, the based subsystem, the multipeak multipeak responses in a trace conditioning are responses in a trace conditioning are possible most probably with equidistant times between the peaks. possible most probably with equidistant times between the peaks.

20

CONCLUSIONS CONCLUSIONS

• The trace conditioning requires an intact hippocampus, because

The trace conditioning requires an intact hippocampus, because of the novelty of

• f the novelty of

complex stimulation, and the considerable difficulty of task req complex stimulation, and the considerable difficulty of task requirements. uirements.

• For model solving such problem the unique timing mechanism is r

For model solving such problem the unique timing mechanism is required so that after equired so that after learning CS learning CS-

• US association system can predict the time of appearance of US w

US association system can predict the time of appearance of US without the ithout the eventual US. The latest new data suggest that such mechanism pa eventual US. The latest new data suggest that such mechanism partially can be found in rtially can be found in hippocampal CA1 hippocampal CA1-

• based subsystem working as a delay line with variable delay time

based subsystem working as a delay line with variable delay times. s.

• The main message of our discussion is that the

The main message of our discussion is that the “ “Neurolocator Neurolocator” ” model, based on the model, based on the hippocampal theory by Vinogradova (2001), can account not only f hippocampal theory by Vinogradova (2001), can account not only for various effects of

• r various effects of

LTM (Kryukov, 2008), but also for trace conditioning as well. LTM (Kryukov, 2008), but also for trace conditioning as well.

• Simultaneously, the CA1 field comparator, much like CA3 field

Simultaneously, the CA1 field comparator, much like CA3 field comparator, can comparator, can compare the septal and cortical inputs, and thereby regulate aro compare the septal and cortical inputs, and thereby regulate arousal and the theta usal and the theta frequency, and monitor the information subsystem frequency, and monitor the information subsystem mPFC mPFC and cerebellum integrated. and cerebellum integrated.

• As a result, the uniform explanation of many conditioning effec

As a result, the uniform explanation of many conditioning effects becomes possible, so ts becomes possible, so that it resolves most of the trace conditioning problems. that it resolves most of the trace conditioning problems.

• The model

The model “ “Neurolocator Neurolocator” ” appended with such CA1 appended with such CA1-

• based subsystem reveals grate

based subsystem reveals grate explanatory strength and predictive power of explanatory strength and predictive power of Vinogradova Vinogradova’ ’s s (2001) Theta (2001) Theta-

• Regulated

Regulated Attention Theory. Attention Theory.

THANK YOU FOR YOUR THANK YOU FOR YOUR ‘ ‘THETA THETA-

• REGULATED ATTENTION

REGULATED ATTENTION’ ’. .

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