prefrontal cortex Flashcards
1. two working memory experiments 2. circuit model
where is prefrontal cortex?
region of the frontal lobe anterior to the motor stripe and the premotor cortex
the anatomical divisio of PFC?
dorsallateral (principal sulcus and regions dorsal to it), orbital, and medial
thalamic projections to PFC?
strong connection between PFC and mediodorsal nucleus;
MD divided into magocellular, parvocellular (project to dorsolateral PFC in primates but not rodent) and paralamellaris regions which project to distinct PFC
Parvocellular MD to dlPFC
Magnocellular MD to orbital medial PFC
Paralamellaris to dorsal PFC (frontal eye fields)
functions of dorsallateral/orbital/medial PFC in clinical sense
DL: selective attention, persevveration, executive function, planning and short-term memory, control of eye movements, speech
orbital: too mush drive, disinhibition
medial: overall reduction in acitivity - apathy, hypokinesia, mutism
pathology of schizophrenia
schizophrenia: associated with alterations in the circuitry of prefrontal cortex, working memory impairment, poor cognitive test related to poor social and occupational functioning
define short-term memory
holding information online that is useful or relevant transiently; it allows behavior to be guided by a representation of a prior stimulus instead of the stimulus itself, and allows the possibility that concepts and plans can govern behavior
two animal studies of working memory
- WGTA: cue presented; during a random delay period cue and choices are not presented; then the animal choose; the modality of WM can change by changing the choice identifier (for spatial working memory)
- ODR: animal trained to fixate on a central target, while fixating a peripheral cue is presented briefly then extinguished; after a rely, whose length can be varied to adjust difficulty, fixation target is extinguished; then animal make saccade to the remembered target location; in the control task, the target never extinguished (duration doesn’t bother the animal in this case)
evidence show that working memory is in PFC
lesions of PFC show a loss of working memory; spatial WM has been localized to the dorsolateral cortex in and adjacent to the principle sulcus
three types of cells that fire during ODR experiment and what’s the property of a neuron’s delay response?
cue cells, delay cells, response cells
an individual neuron’s delay response has a “memory field” - sensitive to direction
working memory is not solely spatial - neurons in inferior convexity responsive to object features (shapes, etc); the different delay responses of neurons in dorsolateral and inferior convexity cortex are correlated with their connections to the dorsal and ventral visual stratums (the where and what pathway, spatial vision and object vision)
summary: responses during delay period is the physiological evidence of working memory
relationship between dopamine and working memory?
prefrontal dopamine depletion impairs working memory (by injection of 6-OHDA and DMI); while increased prefrontal cortical dopamine turnover produced by systemic injection of the antigenic compound impairs working memory - either too little or too much impairs WM; local injection of D1 antagonist disrupts working memory (disrupts performance on spatial delayed response tasks in ODR, but intact in control case)
experiments that show D1R is the main type related to working memory?
iontophoresis in awake behaving animals - when D1 antagonist is applied to a delay neuron, it enhances the memory field of the cell; this effect can be reversed by applying partial D1 agonist;
dose response of D1 antagonist on delay activity - low ejection current enhances memory field, high ejection impairs it - inverse U relationship between D1R occupancy and working memory performance
what are the differences between two types of D1R?
two types of D1R - D1 and D5 are different in dopamine affinity and receptor (NMDA and GABA, LTP and LTD, high and low); both D1 and D5 are found extrasynaptically in overlapping population of pyramidal cell spines and axon terminals, thus D1R are positioned to modulate excitatory glut synapses (D1R overlap in cortical pyramidal cells); distribution of D1R in PV interneuron: more D1 in PV dendrite and axon than D5 (interneurons inhibits pyramidal cells); more D5 in interneurons inhibit other neurons
explain the circuit model
circuit model for the inverted U relationship: no D1R - no augmentation of glut inputs to PN or IN; low D1R - preferentially augments inputs to PN and CR IN (turn on calredin neurons, which turn on pyramidal neuron and turn on their glut activity); mid D1R - beings augment PV IN, further augment PV (starting exciting D1, reduction in pyramidal activity); high D1R - fully augment PV IN (fully stimulate D1 and D5)
need to listen the recording
summary of the circuit model
dopamine controls WM function through D1; inverted U relationship between D1R and WM;
D1R consists of two subtypes;
D1R are present on both pyramidal cells and inhibitory interneurons, and likely involved in PFC circuitry
take home message
PFC involved in variety of cognitive processes;
Working memory is an important function of the PFC that is involved in many cognitive processes;
Response during the delay is the sine qua non of working memory;
This process is applied to the visual modality of both spatial and feature information;
Working memory may involve other modalities;
Without PFC there is no working memory;
Without DA or with too much DA in the PFC there is no working memory;
DA controls working memory function through the D1-family of DA receptors;
There is an inverted U relationship btw D1-family stimulation and working memory;
D1-family has 2 subtypes and they are functionally different;
D1-family are both present on pyramidal cells and inhibitory interneurons, complex actions on PFC circuitry are likely;
