Essentials: The Biology of Aggression, Mating & Arousal | Dr. David Anderson

0:00 Welcome to Huberman Lab Essentials,

0:01 [music] where we revisit past episodes for the most

0:04 potent and actionable science-based [music] tools for mental health,

0:08 physical health, and performance.

0:11 I'm Andrew Huberman, and I'm a professor of neurobiology

0:14 and ophthalmology at Stanford School of Medicine.

0:17 And now, for my discussion with Dr.

0:19 David Anderson.

0:20 David, great to be here and great to finally sit down and chat with you.

0:24 Great to be here, too.

0:24 Thank you so much.

0:25 I want to start with something fairly basic,

0:28 and that's the difference between emotions and states.

0:32 How should we think about them, and why might states be at least,

0:36 as useful a thing to think about, if not more useful?

0:39 The short answer to your question is that I

0:42 see emotions as a type of internal state,

0:46 in the sense that arousal is also a type of internal state,

0:50 motivation is a type of internal state, sleep is a type of internal state.

0:55 They change the input to output transformation of the brain.

1:00 When you're asleep, you don't hear something

1:02 that you would hear if you were awake.

1:04 So, from that broad perspective,

1:07 I see emotion as a class of state that controls behavior.

1:12 The reason I think it's useful to think about it as a state

1:15 is it puts the focus on it as a neurobiological process,

1:21 rather than as a psychological process.

1:24 Many people equate emotion with feeling,

1:27 which is a subjective sense that we can only study in humans,

1:33 because to find out what someone's feeling, you have to ask them,

1:37 and people are the only animals that can talk that we can understand.

1:41 That's how I think about emotion.

1:43 It's the If you think of an iceberg,

1:45 it's the part of the iceberg that's below the surface of the water.

1:50 The feeling part is the tip.

1:52 What are some of the other features of states

1:54 that represent below the tip of the iceberg?

1:57 Right.

1:57 There have been people who have thought

1:58 of emotions as having just really two dimensions,

2:03 a an arousal dimension and a valence dimension.

2:07 Ralph Adolphs and I have tried to expand

2:10 that a little bit to think about components of emotion,

2:14 particularly those that distinguish emotion states from motivational states,

2:19 because they are very closely related.

2:21 One of those important properties is persistence.

2:25 This is something that distinguishes

2:27 state-driven behaviors from simple reflexes.

2:31 Reflexes tend to terminate when the stimulus turns off,

2:36 like the doctor hitting your knee with a hammer.

2:39 It initiates with the stimulus onset,

2:42 and it terminates with the stimulus offset.

2:44 Emotions tend to outlast, often, the stimulus that evoked them.

2:49 If you're walking along a trail here in Southern California,

2:53 you hear a rattlesnake rattling, you're going to jump in the air,

2:57 your heart is going to continue to beat,

2:59 and your palms sweat for a while after it's slithered off in the bush,

3:03 and you're going to be hypervigilant.

3:05 If you see something that even remotely looks snake-like,

3:09 a stick, you're going to stop.

3:11 Not all states have persistence.

3:14 So, for example, you think about hunger.

3:17 Once you've eaten, the state is gone.

3:20 You're not hungry anymore.

3:21 But, if you're really angry and you get into a fight with somebody,

3:25 even after the fight is over,

3:27 you may remain riled up for a long time, and it takes you a while to calm down.

3:34 And then, generalization is an important component

3:38 of emotion states um that uh make them,

3:43 if they have been uh triggered in one situation,

3:47 they can apply to another situation.

3:50 My favorite example of that is you come home from work,

3:53 and your kid is screaming.

3:55 If you had a good day at work, you might pick it up and and soothe it.

3:59 If you had a bad day at work, you might react very differently to it.

4:03 I'd like to talk a bit about aggression,

4:05 the beautiful work of Dayu Lin and others in your lab.

4:08 What are your thoughts on aggression,

4:09 how it's generated, the neural circuit mechanisms,

4:11 and some of the variation in what we call aggression?

4:14 First of all, um the word aggression in my mind refers more

4:20 to a description of behavior than it does to an internal state.

4:26 Aggression could reflect an internal state that we would call anger in humans,

4:32 or could reflect fear, or it could reflect hunger, if it's predatory aggression.

4:39 The work that Dayu did when she was in my lab,

4:42 she found a way to evoke aggression in mice using

4:48 optogenetics to activate specific neurons in a region of the hypothalamus,

4:55 the ventromedial hypothalamus, VMH.

4:58 Following, first, the famous Nobel Prize-winning work of Walter Hess.

5:03 In Hess's original experiments,

5:06 he describes two types of aggression that he evokes from cats,

5:10 depending on where in the hypothalamus he puts his electrode.

5:15 One of which he calls defensive rage.

5:18 That's the ears laid back, teeth bared, and hissing.

5:23 And the other one is predatory aggression,

5:26 where the the cat has its ears forward,

5:29 and it's like batting with its paw at a mouse-like object,

5:33 like it wants to catch it and eat it.

5:35 If you think of ventromedial hypothalamus like a pear sitting on the ground,

5:40 the fat part of the pear and near

5:42 the ground is where the aggression neurons are,

5:44 but the upper part of the pear has fear neurons.

5:48 Fast-forward from that from a lot of work from Dayu now on her own at NYU,

5:53 and with her postdoc Annegret Falkner,

5:56 there's evidence that the type of fighting that we were that we elicit

6:01 when we stimulate VMH is offensive aggression

6:06 that is actually rewarding to male mice.

6:10 They like it.

6:11 They like it.

6:11 Male mice will learn to poke their nose or press a bar

6:16 to get the opportunity to beat up a subordinate male mouse.

6:21 It has a positive valence.

6:24 So, it's become clear that, if you want

6:27 to call it the state of aggressiveness, is multifaceted.

6:33 It depends on the type of aggression,

6:36 and it involves different sorts of circuits.

6:39 Why do you think there would be such a close

6:41 positioning of neurons that can elicit such divergent states and behaviors?

6:47 I mean, you're talking about this pear-shaped

6:49 structure where the neurons that generate

6:51 fear are cheek to jowl with the neurons that generate offensive aggression.

6:56 If you think from an evolutionary perspective,

7:00 it might have been the case that defensive

7:03 behaviors and fear arose before offensive aggression,

7:10 because animals, first and foremost,

7:12 have to defend themselves from predation by other animals.

7:16 And maybe it's only when they're comfortable with having

7:20 warded off predation and made themselves safe that they

7:24 can start about start to think about who's going

7:26 to be the alpha male in in my group here.

7:30 And so, it could be that, if you think that brain regions

7:35 and cell populations evolve by duplication

7:38 and modification of preexisting cell populations,

7:44 that might be the way that those regions wound up next to each other.

7:49 But, I think there must be a functional part, as well.

7:52 So, one thing we know about offensive

7:54 aggression is that strong fear shuts it down.

7:59 Whereas, defensive aggression, at least in rats, is actually enhanced by fear.

8:05 It's one of the big differences

8:07 between defensive aggression and offensive aggression.

8:11 And maybe these two regions are close to each

8:13 other to facilitate inhibition of aggression by the fear neurons.

8:20 We know for a fact that if we deliberately

8:22 stimulate those fear neurons at the top of the pear,

8:26 when two animals are involved in a fight,

8:28 it just stops the fight dead in its tracks,

8:31 and they go off into the corner and freeze.

8:34 So, at least hierarchically,

8:36 it seems like fear is the dominant behavior over offensive aggression.

8:41 I think that's the way I tend to think

8:43 about why these neurons are are all mixed up together.

8:47 And it's not just fight and flight.

8:49 There are also metabolic neurons that are mixed together in VMH, as well.

8:54 One of the concepts that you've raised in your lectures

8:57 before is this idea of a sort of hydraulic pressure.

8:59 Maybe it was Conrad I can't speak now.

9:02 Excuse me.

9:03 Konrad Lorenz, Martin,

9:05 who talked about a kind of hydraulic pressure towards behavior.

9:08 What's really driving hydraulic pressure toward a given state?

9:12 One way that is helpful, at least for me,

9:14 to break this question apart and think about it,

9:17 is to distinguish homeostatic behaviors, that is, need-based behaviors,

9:24 where the pressure is built up because of a need,

9:28 like I'm hungry, I need to eat,

9:31 I'm thirsty, I need to drink, I'm hot, I need to get to a cold place.

9:37 It's basically the thermostat model of your brain.

9:41 You have a set point,

9:42 and then if the temperature gets too hot, you turn on the AC,

9:45 and if the temperature gets too cold, you turn on the heater,

9:48 and you put yourself back to the set point.

9:50 You can think of this accumulated hydraulic pressure

9:54 either being based on something that you were

9:56 deprived of creating an accumulating need or something

10:01 that you want to do building up a drive

10:05 or a pressure to do that and the natural way to think about that at least

10:10 for me is as gradual increases in neural

10:14 activity in a particular region of the brain.

10:18 So for example in the area of the brain of the hypothalamus

10:21 that controls feeding Scott Sternson and others have shown that the hungrier you

10:26 get the higher the level of activity in that region in the brain

10:31 and then when you eat boom the activity goes right back down again.

10:36 And I think in the case of aggression our data

10:38 and others show that the more strongly you drive this region

10:43 of the brain optogenetically the more of just a hair trigger

10:49 you need to set the animal off to get it to fight.

10:52 VMH projects to about 30 different regions in the brain

10:57 and it gets input from about 30 different regions.

11:00 So I kind of see it as both an antenna and a broadcasting center.

11:05 It's like a satellite dish that takes in information from different

11:10 sensory modalities smell maybe vision mechanical mechanical sensation and then

11:17 it sort of synthesizes and integrates that into a fairly low

11:22 dimensional as the computational people call it representation of this pressure

11:28 to attack and it broadcasts that all over the brain

11:32 to trigger all these systems that have to be brought into play

11:36 if the animal is going to engage in aggression because aggression

11:40 is a very risky thing for an animal to engage in.

11:43 It could wind up losing and it could

11:45 wind up getting killed and and so it's brain

11:49 constantly has to make a cost-benefit analysis of whether

11:53 to continue on that path or to back off.

11:56 As we're talking about aggression and mating behavior I think hormones.

12:01 One of the common myths that's out there and I think that persists is

12:05 that testosterone makes animals and humans aggressive

12:09 and estrogen makes animals placid and kind or emotional.

12:13 And as we both know nothing could be further from the truth.

12:17 The specific hormones that are involved in generating

12:19 aggression via VMH are things other than testosterone.

12:25 Can you tell us a little bit more

12:26 about that because there's some interesting surprises in there.

12:28 When we finally identified the neurons in VMH that control aggression

12:34 with a molecular marker we found out that that marker was the estrogen receptor.

12:40 Other labs have shown that the estrogen receptor

12:43 in adult male mice is necessary for aggression.

12:47 If you knock out the gene in VMH they don't fight and it's been shown and a lot

12:52 of this is work from your colleague Nirao

12:54 Shah at Stanford who is one of my former

12:57 PhD students that if you castrate a mouse

13:02 and it loses the ability ability to fight not

13:05 only can you rescue fighting with a testosterone implant

13:10 but you can rescue it with an estrogen implant.

13:12 So you can bypass completely the requirement for testosterone to restore

13:18 aggressiveness to the mice and as you say it's because many

13:22 of the effects of testosterone although not many of them are

13:27 mediated by its conversion to estrogen by a process called aromatization.

13:33 It's carried out by an enzyme called aromatase.

13:37 In fact people may have most of your listeners may have heard of aromatase

13:41 cuz aromatase inhibitors are widely used in female

13:45 humans as adjuvant chemotherapy for breast cancer.

13:49 What's involved in female aggression that's unique

13:52 from the pathways that generate male aggression?

13:55 So we and other labs have studied this in both mice and also in fruit flies.

14:01 One thing in mice that is distinguishes aggression in females from males is

14:06 that male mice are pretty much ready to fight at the drop of a hat.

14:10 Female mice only fight when they are

14:15 nurturing and nursing their pups after they've delivered a litter and there is

14:20 a window there where they become hyper aggressive.

14:24 After the pups are weaned that aggressiveness goes away.

14:27 So this is pretty remarkable that you take a virgin female mouse and expose it

14:34 to a male and her response is to become

14:36 sexually receptive and to mate with him and now

14:39 you let her have her pups and you put the same male or another male mouse

14:44 in the cage with her and instead of trying to mate with him she attacks him.

14:48 We recently showed in a paper this is work from one

14:51 of my students Mong Yu Liu that within VMH in females there are

14:56 two clearly divisible subsets of estrogen receptor neurons and she showed

15:05 that one of those subsets controls fighting and the other one controls mating.

15:10 This gets into the whole issue of neurons

15:13 that are present in females but not in males.

15:16 So this is already showing you some complexity.

15:19 The male mouse VMH has both

15:22 male specific aggression neurons and generic aggression

15:26 neurons and then the female VMH the mating cells are only found in females.

15:31 They are female specific and not found in the male brain

15:35 and so we're trying to find out what these sex specific

15:38 populations of neurons are doing but that indicates that that is

15:41 some of the mechanism by which different sexes show different behaviors.

15:46 If one observes the mating behaviors of different animals we

15:50 know that there's a tremendous range of mating behaviors in humans.

15:53 There can be no aggressive component there can be aggressive component.

15:57 Humans have all sorts of kinks and fetishes and behaviors and most

16:00 of which probably has never been documented cuz most of this happens in private.

16:04 With that said when you look at mating behavior of various

16:07 animals you see an aggressive component sometimes but not always.

16:11 Is it species specific?

16:12 Is it context specific?

16:14 And more generally do you think that there is cross talk between these different

16:18 neuronal populations and the animal itself might

16:21 be kind of confused about what's going on?

16:23 I can't really speak to the issue of whether this is

16:26 species specific cuz I'm not a naturalist or a zoologist.

16:30 I've seen like you have in the wild for example lions when they mate.

16:35 I've seen them in Africa there's often a biting component of that as well.

16:39 One of the things that surprised us when we

16:42 identified neurons in VMHVL that control aggression in males is

16:48 that within that population there is a subset of neurons

16:53 that is activated by females during male female mating encounters.

16:58 There's some evidence that those female selective neurons

17:03 in VMH are part of the mating behavior.

17:08 If you shut them down the animals

17:10 don't mate as effectively as they otherwise would.

17:14 What happens when you stimulate them we don't yet know because we don't

17:18 have a way to specifically do

17:20 that without activating the male aggression neurons.

17:24 But I think they must be there for a reason because VMH is

17:28 not traditionally the brain region to which

17:31 male sexual behavior has been assigned.

17:35 That's another area called the medial preoptic area and there we

17:39 have shown that there are neurons that definitely stimulate mating behavior.

17:45 In fact if we activate those mating neurons in a male

17:48 while it's in the middle of attacking another male it

17:51 will stop fighting start singing to that male and start

17:56 to try to mount that male until we shut those neurons off.

17:59 So those are the make love not war neurons

18:03 and VMH are the make war not love neurons and there

18:06 are dense interconnections between these two nuclei which are

18:11 very close to each other into the in the brain.

18:14 But it's also possible that there are some

18:17 cooperative interactions between those structures as well as antagonistic

18:23 interactions and the balance of whether it's the cooperative

18:27 or antagonistic interactions that are firing at any given

18:31 moment in a mating encounter as you suggest

18:35 may determine whether a moment of of of coital

18:41 bliss among two lions may suddenly turn into a snap

18:46 or a growl and a bearing of fangs.

18:49 We don't know that but certainly the substrate

18:52 the wiring is there for that to happen.

18:55 When we made that discovery initially it

18:57 it raised the question in my mind whether

19:00 some people that are serial rapists for example

19:05 and engage in sexual violence might in some

19:08 level have their wires crossed in some

19:11 way that that these states that are supposed

19:13 to be pretty much separated and mutually antagonistic

19:17 are not and are actually more rewarding and reinforcing.

19:21 I'd love to talk about this structure cuz seems to be

19:24 involved in everything which is the PAG the periaqueductal gray.

19:29 It's been studied in the context of pain.

19:30 It's been studied in the context

19:32 of the so called lordosis response the the receptivity

19:35 or arching of the back of the female

19:36 to receive intromission and mating from the male.

19:39 In particular I want to know is there some mechanism

19:42 of pain modulation and control during fighting and or mating.

19:48 And the reason I ask is that while I'm not combat

19:52 sports person years ago I did did a little bit of martial

19:55 arts and it always was impressive to me how little it hurt

19:58 to get punched during a fight and how much it hurt afterwards.

20:02 Right?

20:03 So there's clearly a some endogenous pain control

20:06 that then wears off and then you feel beat up.

20:09 Yep.

20:09 What's PAG doing vis-a-vis pain and what's

20:12 pain doing vis-a-vis these other behaviors?

20:14 So I think of PAG like a old-fashioned telephone switchboard.

20:20 There are calls coming in and then the cables have to be

20:24 punched into the right hole to get the information to be routed

20:28 to the right recipient on the other end of it because pretty much

20:32 every type of innate behavior you can think of has had the PAG implicated.

20:38 In cross-section the PAG kind of looks like the water

20:41 in a toilet when you're standing over an open toilet bowl.

20:45 And if you imagine a clock face projected on to that, it's

20:51 like the PAG has sectors from 1 to 12

20:55 maybe even more of them and in each of those sectors

20:58 you find different neurons from the hypothalamus are projecting.

21:02 So could turn out that there is a topographic arrangement

21:06 along the dorsal ventral axis of the PAG and the medial

21:10 lateral axis of the PAG that determines the type of behavior

21:15 that will be emitted when neurons in that region are stimulated.

21:19 And I think sort of all of the evidence is pointing

21:22 in that direction but by no means has it been mapped out.

21:26 Now the thing that you mentioned about it not

21:28 hurting when you got beat up during martial arts,

21:32 there is a well-known phenomenon called fear-induced analgesia

21:38 where when an animal is in a high state of fear like if it's trying to defend

21:45 itself there is a suppression of pain responses.

21:51 And I'm not sure completely about the mechanisms and how well

21:56 that's understood but for example the adrenal gland has a peptide

22:01 in it that is released from the adrenal medulla which controls

22:06 the fight or flight responses and that peptide has analgesic activities.

22:12 Now whether peptide is?

22:14 bovine adrenal medullary peptide of 22 amino acid residues and I

22:19 only know about it because it activates a receptor that we discovered

22:24 many years ago that's involved in pain and we thought it

22:27 promoted pain but it turns out that it this actually inhibits pain.

22:31 It's like an endogenous analgesic.

22:34 Whether this is happening this type of analgesia is happening when

22:39 an animal is engaged in offensive aggression or in mating behavior,

22:46 I don't know but it certainly is possible and I

22:49 don't know whether these analgesic mechanisms are happening in the PAG.

22:55 They could also be happening a little further down in the spinal cord.

22:59 The PAG is really continuous with the spinal cord.

23:02 If you just follow it down towards the tail of an animal,

23:06 you will wind up in the spinal cord and so it could be that there are

23:11 influences acting at many levels on pain

23:14 in the PAG and in the spinal cord as well.

23:17 And it may well be known.

23:19 I just don't know it.

23:20 I want to distinguish clearly between things that are not known that I

23:24 know are unknown which is in a fairly small area where I

23:28 have expertise from things that may be known but I'm ignorant of them

23:33 because I just don't have a broad enough knowledge base to know that.

23:36 Tell us about tachykinin.

23:38 I've talked about this a couple times on different

23:40 podcast episodes because of its relationship to social isolation.

23:45 My understanding is that tachykinin is present in flies and mice

23:48 and in humans and may do similar things in those species.

23:53 So tachykinin is refers to a family of related neuropeptides.

23:59 So these are brain chemicals.

24:01 They're different from dopamine and serotonin

24:05 in that they're not small organic molecules.

24:08 They're actually short pieces of protein that are directly encoded

24:13 by genes that are active in specific neurons and not

24:17 in others and when those neurons are active those neuropeptides

24:21 are released together with classical transmitters like glutamate, whatever.

24:26 Tachykinins have been famously implicated in pain,

24:30 particularly tachykinin 1 which is called substance P,

24:36 one of the original pain modulating.

24:39 This is something that promotes inflammatory pain.

24:42 And so we did a screen,

24:45 unbiased screen of peptides and found indeed that one of the tachykinins,

24:50 Drosophila tachykinin, those neurons when you activate them strongly promote

24:56 aggression and it depends on the release of tachykinin.

24:59 Now the interesting thing is that in flies just like in people

25:04 and practically any other social animal

25:07 that shows aggression social isolation increases aggressiveness.

25:12 So putting a violent prisoner in solitary confinement is absolutely

25:16 the worst most counterproductive thing you could do to them.

25:20 And indeed we found in flies

25:22 that social isolation increases the level of tachykinin

25:27 in the brain and if we shut that gene

25:29 down it prevents the isolation from increasing aggression.

25:33 So since my lab also works on mice,

25:36 it was natural to see whether tachykinins might be upregulated

25:42 in social isolation and whether they play a role in aggression.

25:45 And this is work done by a former post-doc Muriel Zelakowski

25:49 now at University of Salt Lake City in Utah and she

25:52 found remarkably that when mice are socially isolated for 2 weeks

25:58 there is this massive upregulation of tachykinin 2 in their brain.

26:04 In fact, if you tag the peptide

26:07 with a green fluorescent protein from a jellyfish genetically,

26:12 the brain looks green when the mice are socially

26:15 isolated cuz there's so much of this stuff released.

26:18 And she went on to show that that increase

26:23 in tachykinin is responsible for the effect

26:27 of social isolation to increase aggressiveness

26:31 and to increase fear and to increase anxiety.

26:34 And in fact there are drugs that block

26:37 the receptor for tachykinin which were tested

26:40 in humans and abandoned because they had no

26:43 efficacy in the test that they were analyzed for.

26:46 If you give those drugs to a socially isolated mouse,

26:50 it blocks all of the effects of social isolation.

26:54 It blocks the aggression,

26:56 it blocks the increased fear and the increased anxiety.

27:00 And that Muriel described it, the mice just looked chill.

27:03 It's not a sedative which is really important.

27:06 It's not that the mice are going to sleep.

27:09 Most remarkably is once you socially isolate a mouse

27:14 and it becomes aggressive you can never put

27:16 it back in its cage with its brothers

27:20 from its litter because it will kill them all overnight.

27:23 But if you give it this drug which is called

27:26 osanetant that black blocks tachykinin 2 that mouse can be returned

27:32 to the cage with its brothers and will not attack them

27:36 and seems to be happy about that for the rest of the time.

27:39 So this is an incredibly powerful effect

27:43 of this drug and I've been really interested in trying

27:46 to get pharmaceutical companies to test this drug

27:50 which has a really good safety profile in humans

27:54 in testing it in people who are subjected

27:57 to social isolation stress or bereavement stress but it's

28:02 just very difficult for economic reasons to find

28:05 a way to get somebody to test that.

28:07 As long as we're talking about humans I'd love

28:09 to get your thoughts about human studies of emotion.

28:11 I know you wrote this book with Ralph Adolph so you have this new book.

28:14 There are books that are worth reading

28:16 and then there are books that are important

28:17 and I think this book is truly important

28:19 for the general population to read and understand.

28:21 There's a heat map diagram in that book of subjective reports

28:25 that people gave of where they experience an emotion or a feeling,

28:31 somatic feeling, in their body or in their head or both when they are angry,

28:36 sad, calm, lonely etc.

28:39 etc.

28:40 And I wouldn't want people to think that those heat

28:42 maps were generated by any physiological measurement because they were not.

28:48 How should we think about the body in terms of states?

28:51 And at some point I'd love for you to comment on that heat map experiment.

28:55 This goes back to something called the somatic marker hypothesis

29:00 that was proposed by Antonio Damasio who was a neurologist at USC.

29:05 The idea that our subjective feeling

29:09 of a particular emotion is in part associated

29:14 with a sensation of something happening in a particular

29:19 part of our body, the gut, the heart.

29:23 If there is a physiology underlying these heat maps

29:26 it could reflect increased blood flow to these different

29:29 structures and that in turn reflects communication between

29:34 the brain and the body and it's bidirectional communication.

29:38 And it's mediated by the peripheral nervous system,

29:43 the sympathetic and the parasympathetic nervous system which control heart rate,

29:48 for example, blood vessel, blood pressure.

29:51 And those neurons receive input

29:54 from the hypothalamus and other blood brain region,

29:58 central brain regions that control their activity.

30:01 And when the brain is put in a particular state,

30:06 it activates sympathetic and parasympathetic neurons,

30:10 which have effects on the heart and on blood pressure.

30:14 These in turn feed back onto the brain through the sensory system.

30:20 And a large part of this bidirectional

30:23 communication is also mediated through the vagus nerve,

30:27 which many of your listeners and viewers may have heard

30:30 about because it's become a topic of intense activity now.

30:34 The vagus nerve is a bundle of nerve

30:38 fibers that comes out basically of your skull,

30:42 out of the central nervous system, and then sends fibers in to your heart,

30:50 your gut, all sorts of visceral organs.

30:53 That information is both afferent and efferent.

30:57 The vagal fibers sense things that are happening in the body.

31:03 So, when you're The reason you feel your stomach tied up in knots if

31:08 you're tense is that those vagal fibers

31:11 are sensing the contraction of the gut muscles.

31:15 They're also afferents, which means that information coming out of the brain

31:20 can influence those peripheral organs as well.

31:23 And there's work from a number of labs just in the last 6 months or so,

31:29 where people are starting to decode the components

31:33 of the different fibers in the vagus nerve.

31:37 And it's amazing how much specificity is.

31:40 There are specific vagal nerves that go to the lung,

31:44 that control breathing responses, that go to the gut, that go to other organs.

31:50 It's almost like a set of color-coded lines, labeled lines for those things.

31:56 And now how those vagal afferents play a role in the playing out of emotion

32:04 states is a fascinating question that people

32:07 are just beginning to scrape the surface of.

32:10 But I think what's exciting now is that people are

32:13 going to be developing tools that will allow us to turn

32:16 on or turn off specific subsets of fibers within

32:21 the vagus nerve and ask how that affects particular emotional behaviors.

32:25 So, you're absolutely right.

32:27 This brain-body connection is critical, not just for the gut, but for the heart,

32:32 for the lungs, for all kinds of other parts of your body.

32:36 And Darwin recognized that as well.

32:39 And I think it's it's a central feature of emotion state.

32:43 And I think what underlies our subjective feelings of an emotion.

32:48 David, I have to say as a true fan of the work

32:51 that your lab has been doing over so many decades,

32:54 I know I speak on behalf of a tremendous number of people when I say thank

32:58 you for taking time out of your important

33:00 schedule to share with us what you've learned.

33:02 I really have appreciated your questions.

33:05 They're all They've all been right on the money.

33:07 You've hit all of the critical important issues in this field,

33:11 and you've you've uncovered what is known,

33:15 the little bit is known, and how much is not known.

33:18 And I think it's important to emphasize the unknown things

33:23 because that's what the next generation of neuroscientists has to solve.

33:28 And so, I hope this will help to attract

33:30 young people into this field because it's so important,

33:34 particularly for our understanding of mental

33:36 illness and mental health and and psychiatry.

33:41 We've got to figure out how emotion systems are controlled in a causal way

33:47 if we ever want to improve on the psychiatric treatments that we have now.

33:52 And that's going to require the next generation of people coming into the field.

33:56 Absolutely.

33:57 I second that.

33:58 Well, thank you.

33:59 It's been a delight.

34:00 Thank you.

34:03 [music] Great.

34:02 Really appreciate it.

34:06 [music]