FEB 13

Question 1

internal states

Answer 1

hidden processes in the brain that influence perception, cognition and action

include EMOTION, arousal, motivation, homeostatic needs (hunger, thirst)

Question 2

how can we study internal states?

Answer 2

1. observe them directly (observe directly, experimentally manipulate)
2. infer through changes in: behaviour, physiology, processes within the brain

Question 3

“internal states consist of changes in nervous system function that can be inferred from…”

Answer 3

behaviour

Question 4

features of internal states

Answer 4

scalability

generalization

persistence

valence

pleiotropy

(similar to A&A’s conception of central emotion states)

Question 5

small subsets of neurons can drive…

Answer 5

(internal) state transitions

Question 6

example of small set of neurons driving state transitions

Answer 6

briefly activating certain neurons via optogenetics leads to

1. specific BEHAVIOURAL activity
2. specific activity within CERTAIN NEURAL CIRCUITS

ie. stimulation of thirst regulating neurons leads to LICKING (thirst indicative behaviour) and also to RECAPITULATION OF BRAIN WIDE NERUAL ACTIVITY

Question 7

can internal states influence activity in large parts of the brain?

Answer 7

YES

confirmed by OPTICAL and ELECTRICAL RECORDING techniques for LARGE SCALE recording of neurons across MULTIPLE brain REGIONS

ie. LARGE, WIDESPREAD changes in brain activity when animal is MOVING, versus CALM & STILL

Question 8

the widespread changes in brain activity associated with different behaviours in animals could be either…

Answer 8

1. a MECHANISM of internal states
2. a MOTOR FEEDBACK SIGNAL in the brain tracking actions

(^ maybe it’s just about motor behaviour associated with action, and has nothing to do with the behavioural state)

(or a COMBO of the two)

Question 9

internal states influencing neurons across the brain - what remains to be seen?

Answer 9

“remains to be seen whether such brain-wide concerted activity patterns are important for the EXECUTION of state-dependent behaviour, or are a MERE CONSEQUENCE of SHARED ACTIVITY across recurrently connected circuits that span multiple brain regions”

Question 10

what are particularly well positioned to modulate internal states?

Answer 10

neuromodulatory systems

Question 11

why are neuromodulators well position to modulate internal states?

Answer 11

1. neuromodulators modulate SYNAPTIC and CELLULAR function over LONG TIME SCALES

^ because they influence BIOCHEMICAL SIGNALLING and ION CHANNEL FUNCTION

2. neuromodulator effects can SCALE with the magnitude of neuromodulator released
3. can act LOCALLY or send signals across MULTIPLE BRAIN REGIONS

^ these properties make them well-suited to FLEXIBLE, SCALABLE and PERSISTENT control of behaviour that’s central to internal states

Question 12

2 main reasons why neuromodulators are well suited to internal states

Answer 12

1. LONG TIME SCALES (persistence)
2. they SCALE with stimulus intensity (scalability)
3. can send signals LOCALLY or across MULTIPLE REGIONS (pleiotropy)

Question 13

some commonn neuromodulators

Answer 13

dopamine

serotonin

acetylcholine

histamine

oxytocin

Question 14

Panksepp and neuromodulators

Answer 14

Panksepp wanted to map basic emotion states to specific neuromodulators

ie. SEEKING and DOPMAINE

shows that the neuromodulatory idea of controlling internal states has a long history

Question 15

neuromodulatory systems have what type of organization?

Answer 15

fan-in, fan-out

(like A & A’s architecture)

Question 16

explain how neuromodulators have a fan-in, fan-out organization

Answer 16

1. small number of cells that release neuromodulators RECEIVE INPUTS from MANY DIFF BRAIN AREAS
2. these cells then RELEASE their neuromodulator in MULTIPLE BRAIN REGIONS

^ this org allows neuromodulators to have MULTIPLE, PARALLEL EFFECTS

Question 17

what does fan-in, fan-out organization of neuromodulators allow for?

Answer 17

allows them to have MULTIPLE EFFECTS

pleiotropy

Question 18

time scale of neuromodulatory signaling

Answer 18

seconds to hours

Question 19

neuromodulatory target regions

Answer 19

very spread out across the brain

diverse effects

intracellular signalling and biochemical signalling cascades

Question 20

emerging themes of internal state control across ________

Answer 20

species

NUMBER OF COMMONALITIES across species have emerged

suggest SEVERAL COMMON NEURAL MECHANISMS that contribute to internal state control

4 themes

Question 21

theme 1: internal states influence multiple circuits and cell types in parallel

Answer 21

while there’s a predominant view for a fan-in, fan-out mechanism for internal states…

there’s also evidence of DISPERSED, DISTRIBUTED, PARALLEL ACTION

^ in this view, neuromodulators exert state-like effects on behaviour across a number of brain regions, at the same time but separately

Question 22

in contrast to the fan-in, fan-out view, neuromodulators may exert state like effects on behaviour how?

Answer 22

at the SAME TIME

across a NUMBER OF REGIONS

but SEPARATELY

(visualized as a web with a central node, or with many tiny groupings of nodes)

Question 23

example of dispersed/distributed parallel action of neuromodulators

Answer 23

(in contrast to fan-in, fan-out view)

Tac2 controls effects of SOCIAL ISOLATION STRESS

Tac2 mediates effects of social isolation on:
1. AGGRESSION
2. ACUTE FEAR
3. PERSISTENT FEAR

^ each of these effects is controlled by a DIFFERENT BRAIN REGION

so many a single neuromodulator (Tac2) type is acting across distributed brain regions in response to social isolation stress

Question 24

theme 2: neuromodulators act in concert

Answer 24

usually there’s an interaction of MULTIPLE neuromodulators

ie. many neuromodulators at work in PARALLEL during social isolation stress

Question 25

theme 3: state transitions engage mutually-exclusive neural populations

Answer 25

ie. DWELLING versus ROAMING neural populations the 2 populations are ON-OFF switches 2 populations are DISCRETELY ACTIVATED - population A and population B have no overlap avoid versus explore

Question 26

theme 4: persistence through recurring dynamics

Answer 26

neural circuit arrangement can support STABLE, SUSTAINED RESPONDING to TRANSIENT STIMULI

Question 27

example of theme 4: persistence through recurring dynamics

Answer 27

1. in Drosophila, activation of pC1 neurons in females increases receptivity to males for SEVERAL MINS after OPTOGENETIC STIMULATION (persistent state) 2. imaging shows that stimulating pC1 neurons INCREASES ACTIVITY in many DOWNSTREAM BRAIN AREAS (increases network activity 3. connectivity analyses show that pC1 neurons are wired in a RECURRENT NEURAL CIRCUIT with other EXCITATORY NEURONS ^ this explains how brief stimulation leads to sustained activity

Question 28

how can we explain fact that brief stimulation leads to sustained activity?

Answer 28

if neurons are wired in a recurrent neural circuit with other excitatory neurons ie. cP1 neurons in Drosophila

Question 29

4 themes that have been gathered from examining neuromodulators as behind internal states

Answer 29

1. internal states influence multiple circuits and cell types in parallels 2. neuromodulators act in concert 3. state transitions engage mutually-exclusive neural populations 4. persistence through recurrent dynamics

Question 30

the fact that internal states are persistent says what about neural activity?

Answer 30

reflects persistent changes in neural activity there's at least 2 mechanisms for persistent changes in neural activity...

Question 31

2 mechanisms for persistent changes in neural activity

Answer 31

1. NEUROMODULATORY SIGNALLING (long time scales, fan-out effects) 2. RECURRENT NEURAL CIRCUITS (excitatory neuronal circuits)

Question 32

paper's concluding questions

Answer 32

are brain wide neural states causal to internal states or a consequences of the interconnectedness of the brain? how do different states interact? why are different states associated with distinct circuit motifs (fan-in, fan-out versus web)? when do brain, behaviour, and physiological measurements reflect the same versus distinct internal states?

Question 33

paper's final quote

Answer 33

"these questions and more can be addressed using the emerging methodological approaches discussed herein... ...including more rigorous quantification of states using integrated datasets and ML approaches... ...precise observation and control of electrical and biochemical activity across entire nervous systems... ...and better theoretical frameworks understanding the utility of internal states" ^ comes back to the computational level here in the conclusion, but this is really a neuron-first perspective (implementation level)