Neuro Box 5

At a neural level, research suggests that the long-term consequences of uncontrollable stimulation depend upon a region of the midbrain known as the——

dorsal raphe nucleus (DRN).

The DRN lies just ventral to another key region ——-

the periaqueductal gray (PAG),

the DRN can regulate neural activity in other regions of the central nervous system through neurons that release ——

the neurotransmitter serotonin (5-HT)

the DRN can regulate neural activity in other regions of the central nervous system through neurons that release the neurotransmitter serotonin (5-HT)

these 5-HT neurons project to regions implicated in——-

stress and helplessness

exposure to uncontrollable shock activates 5-HT neurons within the DRN and ———-

has a sensitizing effect, enhancing the amount of 5-HT released at distant sites

exposure to uncontrollable shock activates 5-HT neurons within the DRN and has a sensitizing effect, enhancing the amount of 5-HT released at distant sites

• Importantly, these effects are not observed after ——

• an equivalent exposure to controllable stimulation

pharmacologically inhibiting the DRN during uncontrollable stimulation ——the induction of learned helplessness

BLOCKED

pharmacologically ——- the DRN had a behavioral effect similar to that observed after uncontrollable stimulation

ACTIVATING

— —— is both necessary and sufficient to produce learned helplessness.

the activation of the DRN

Maier and Watkins hypothesized that behavioral control regulates DRN activity through neurons that project from the ——- and  ——- regions of the ventral medial prefrontal cortex (vmPFC)

- prelimbic (and) infralimbic

Maier and Watkins hypothesized that behavioral control regulates DRN activity through neurons that project from the prelimbic and infralimbic regions of the ——

(of the) ventral medial prefrontal cortex (vmPFC)

Maier and Watkins hypothesized that behavioral control regulates DRN activity through neurons that project from the prelimbic and infralimbic regions of the ventral medial prefrontal cortex (vmPFC)

• These excitatory neurons engage ——- within the DRN that have an —-effect.

• GABAergic interneurons ,    inhibitory

Maier and Watkins hypothesized that behavioral control regulates DRN activity through neurons that project from the prelimbic and infralimbic regions of the ventral medial prefrontal cortex (vmPFC)

• These excitatory neurons engage GABAergic interneurons within the DRN that have an inhibitory effect.

  • As a result, pharmacological activating the vmPFC →

• inhibits 5-HT neural activity within the DNR and blocks the development of learned helplessness

If behavioral control inhibits the DNR through the vmPFC, then pharmacologically disrupting vmPFC function should →

eliminate the protective effect of instrumental control

Minus the dampening action of the vmPFC input, controllable aversive stimulation should engage 5-HT neurons within the DNR and →

paradoxically produce a helplessness-like effect.

One of the most interesting and clinically relevant features of behavioral control is that it has a lasting effect that ——

behaviorally immunizes the organism from becoming helpless when later exposed to uncontrollable stimulation

What process plays a key role in behaviorally immunizing the organism from becoming helpless when later exposed to uncontrollable stimulation?

The vmPFC does

vmPFC inhibited during uncontrollable stimulation →

the protective effect was not observed

Minus the vmPFC, uncontrollable shock induced helpless in subjects that —-

had previously received controllable stimulation.

activating the vmPFC will ——

(will) prevent uncontrollable shock from inducing helplessness

The stronger claim is that the vmPFC will, when combined with shock input ——

induce a long- term effect analogous to that produced by instrumental control.

combining vmPFC activation with uncontrollable shock yielded →

an effect equivalent to controllable stimulation, engaging a protective effect that blocked the subsequent induction of helplessness.

— —— and ——— also have divergent effects on Pavlovian fear conditioning

Controllable (and) uncontrollable stimulation

Uncontrollable stimulation generally—-

enhances conditioning

controllable stimulation generally ——- conditioning

inhibits

fear conditioning depends upon neurons within the ——-.

amygdala

fear conditioning depends upon neurons within the amygdala.

• Input from the CS and US appear to be associated within the —- region

basolateral

fear conditioning depends upon neurons within the amygdala.

• Input from the CS and US appear to be associated within the basolateral region while the performance of the CR is orchestrated by the ——.

central nucleus

fear conditioning depends upon neurons within the amygdala.

• Input from the CS and US appear to be associated within the basolateral region while the performance of the CR is orchestrated by the central nucleus.

  • uncontrollable stimulation enhances —— through 5-HT neurons that project to the basolateral amygdala

fear-related CRs

The calming effect of controllable stimulation has been linked again to the vmPFC and, more specifically, to the ——-

infralimbic region

The calming effect of controllable stimulation has been linked again to the vmPFC and, more specifically, to the infralimbic region which sends a projection to the ——— of the amygdala

intercalated cell region

The calming effect of controllable stimulation has been linked again to the vmPFC and, more specifically, to the infralimbic region which sends a projection to the intercalated cell region of the amygdala

• this portion of the amygdala is composed of ——— cells that project to the ——-

inhibitory (GABAergic) , (to the) central nucleus

The calming effect of controllable stimulation has been linked again to the vmPFC and, more specifically, to the infralimbic region which sends a projection to the intercalated cell region of the amygdala

• this portion of the amygdala is composed of inhibitory (GABAergic) cells that project to the central nucleus

• Consequently, engaging the infralimbic region→

inhibits the output from the central nucleus and fear behaviors

The calming effect of controllable stimulation has been linked again to the vmPFC and, more specifically, to the infralimbic region which sends a projection to the intercalated cell region of the amygdala

• this portion of the amygdala is composed of inhibitory (GABAergic) cells that project to the central nucleus

• Consequently, engaging the infralimbic region inhibits the output from the central nucleus and fear behaviors

  • Given these observations, Maier and his colleagues hypothesized that ——— acts to inhibit the performance of fear-elicited CRs (within the central nucleus) rather than learning (within the basolateral nucleus)

• output from the infralimbic area of the vmPFC

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by ——

administering the GABA agonist muscimol, either before conditioning or testing

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• In rats that received the drug vehicle alone:

the usual pattern of results was obtained; controllable shock reduced behavioral signs of fear whereas prior exposure to uncontrollable shock enhanced conditioned freezing

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• In rats that received the drug vehicle alone: the usual pattern of results was obtained;

; controllable shock reduced behavioral signs of fear whereas prior exposure to uncontrollable shock enhanced conditioned freezing

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• Inhibiting the infralimbic region prior to conditioning:

had no effect, suggesting that behavioral control does not affect learning.

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• Inhibiting the infralimbic region prior to conditioning: had no effect, suggesting that behavioral control (does/ does NOT?) affect learning.

does NOT

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• Turning off the infralimbic region prior to testing:

had little effect on rats that had received uncontrollable shock, but eliminated the calming (anti-fear) effect of controllable shock

hypothesized that output from the infralimbic area of the vmPFC acts to inhibit the performance of fear-elicited CRs (within the central nucleus)

- To explore this idea, rats were given controllable or uncontrollable shock & A third group remained untreated

- Rats were conditioned a week later by administering shock in a novel context. The next day, they tested whether the context elicited conditioned fear (freezing).

- To explore the role of the infralimbic area, they inactivated this region in half the subjects by administering the GABA agonist muscimol, either before conditioning or testing

• In rats that received the drug vehicle alone: the usual pattern of results was obtained; controllable shock reduced behavioral signs of fear whereas prior exposure to uncontrollable shock enhanced conditioned freezing

• Inhibiting the infralimbic region prior to conditioning: had no effect, suggesting that behavioral control does not affect learning.

• Turning off the infralimbic region prior to testing: had little effect on rats that had received uncontrollable shock, but eliminated the calming (anti-fear) effect of controllable shock

it appears that a history of behavioral control reduces ——-, but not its ——

the expression of fear, (not) acquisition