NEURAL CIRCUITS Flashcards

1
Q

What are the key brain areas involved in visual information processing?

A

Right hemifield activates left brain and vice versa
Primary Visual Cortex has two information streams
- Dorsal “where” spatial location stream along posterior parietal lobe
- Ventral “what” object feature stream along inferior temporal lobe

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2
Q

Which part of the retina has the highest acuity?

A

Fovea has the highest

The rest of the retina has smaller acuity and contains primarily rods

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3
Q

What are the two layers in the retina?

A

Outer plexiform - photoreceptor, bipolar and horizontal cells
Inner plexiform - bipolar, amacrine and ganglion cells

Horizontal and amacrine cells are inhibitory interneurons

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4
Q

Describe the photo transduction cascade that leads to photoreceptors hyperpolarising in light?

A

Opsin receptor activated and undergoes conformational change to activate GPCRs
Ga activates phosphodiesterase which breaks down cGMP causes channels to close
No cations can diffuse in so cell hyperpolarise

*Photo transduction occurs in the outer segment of the photoreceptor
Rods become active at dim light
Cones become active at bright light

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5
Q

What is the difference between on and off centre cells?

How is visual processing transferred from photoreceptor to ganglion cells?

A

In the light, photoreceptors become hyperpolarised (release less glutamate) and become more depolarised in the dark (release more glutamate)
Horizontal cell releases inhibitory neurotransmitter onto centre photoreceptor if binds surround is dark and releases glutamate

“On centre cell” - contain metabotropic glutamate receptor and hyperpolarise in response to glutamate, depolarise if no glutamate
“Off centre cell” - contain ionotropic glutamate, depolarise when glutamate bind, hyperpolarise in absence of glutamate

ON centre ganglion cells receive excitatory input from ON centre bipolar cells
OFF centre ganglion cells receive excitatory input from OFF centre bipolar cells

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6
Q

As olfactory sensory neurons mature, they narrow down to express a single olfactory receptor each
Olfactory sensory neurons expressing same receptor converge on the same glomerulus
*In Drosophila, sensory neurons on antennae send axons to the antennal lobe (version of the olfactory bulb in humans)

Receptor specific matching of sensory neurons to second-order neurons ensure odour specificity is carried through
What is the pathway of olfactory neurons in drosophila and mammals?

A

Drosophila:
Olfactory receptor neurons –> glomeruli –> projection neurons

Mammals:
Olfactory sensory neurons –> glomeruli –> mitral cells, tufted cells

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7
Q

How does the first relay synapse transform odour code

A
  • Synaptic adaptation emphasises start of odour - as weakens over time e.g. neurotransmitter running out
  • Converging sensory neurons onto second order neuron reduces noise and strengthens weak response
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8
Q

What does interglomerular cross talk achieve?

A
  • Gain control - sensitivity to both weak and strong odours

- De-correlations - make responses of neuronal population to different odours as different as possible

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9
Q

What areas of the brain (in humans and insects) regulate learned and innate behaviour?

A

In human
- learned behaviour regulated by Pisiform Cortex
- innate behaviour by Amygdala
In insect
- learned behaviour by mushroom body (Kenyon cells)
- innate behaviour by lateral horn

Silencing of amygdala –> mice no longer avoid fox odour TMT
Silencing of lateral horn –> fruit flies no longer avoid laying eggs on food that smells of toxic microbes

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10
Q

Taste circuits also show lateral inhibition

What is the order of taste circuits?

A

Taste buds –> Solitary nucleus of brainstem –> VPM* –> Insula and parietal cortex

*Ventral posterior medial nucleus of thalamus

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11
Q

What is the difference between innate and learning circuitry?

A

Innate Learned
Purpose Categorise Discriminate
Activity Dense codes Sparse codes
Odours? Certain preferred Arbitrary
Connectivity Stereotyped Random

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12
Q

Sensing sound is important as…

A
  • Early mammals were small and nocturnal so relied on sound for survival and finding food
  • Evolved massive range of frequency and intensity sensitivity
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13
Q

What features of sound need encoding?

A
  • SOUND FREQUENCY - Hz - achieved by cochlear mechanics and physiology of hair cells - range (x10^3)
  • SOUND INTENSITY (Loudness) - achieved by the firing rates of many ANFs (Auditory Nerve Fibres)
  • ONSET - rapid onset important for localising different sounds and creating a topographic map of auditory space
  • DURATION - ear cannot fatigue so sensory cell synapses are specialised for sustaining high rates of neurotransmitter release
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14
Q

Describe fluid composition of Scala Vestibuli (SV), Scala Media or Cochlear Duct (SM) and Scala Tympani (ST)

A

Scala Vestibuli (SV) and Scala Tympani (ST) contain perilymph - low K+ @5mM, normal Ca2+ @1.3mM

Scala Media (SM) or Cochlear Duct contains endolymph - high K+ @150mM, low Ca2+ @20μM
*Active pumping of ions through Stria Vascularis into Scala Media creates positive potential
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15
Q

The tonotopicity of the mammalian cochlea is established by the Basilar Membrane
The base of the BM is narrow and stiff so is moved by high frequency stimulation
Whereas, the apex of the BM is wide and flopping, moved by low frequency stimulation

How does movement of the basilar membrane convert sound into neuronal signals

*BF = maximal stimulation

A

Excitatory deflection
- Basilar membrane displaces hair bundles creating maximal tip tension and opening MET (Mechanoelectrical Transducer) channels
K+ ions diffuse in from Scala Vestibuli endolymph and Caa2+ in from Scala Tympani depolarising hair cell and creating action potentials in afferent fibres

*Inhibitory deflection causing large deflection of hair bundle in opposite direction and maximal tip link tension which closes MET current
This fully hyperpolarises hair cell below resting potential creating no or very few action potentials

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16
Q

What is the difference between inner and outer hair cells?

A

IHCs are the main sensory receptors of the cochlea. The sound induced receptor potential causes neurotransmitter release onto spiral ganglion neurons
- more K+ channels

OHC receptor potential activates electromotility that enhances the mechanical stimulation of IHCs and improves tuning into cochlea - cochlear amplifier

  • Prestin in cell membrane required for electromotility
  • V shaped hair bundle
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17
Q

What are the different afferent neurons in the cochlea?

A

Type I - innervate IHCs (95% of all afferents)

  • Each IHC has 10-30 type I fibres
  • Carry all sound information from the IHCs to cochlear nucleus

Type II - innervate OHCs (5% of all afferents)

  • Turn basally to innervate higher frequency OHCs
  • Branched - contact up to 30 OHCs - also synapse in the cochlear nucleus
  • Function not known for sure - thought to be related to nociception in the cochlea caused by damage/overstimulation
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18
Q

Identify the key brain areas involved in visual object recognition

A

Retinal ganglion cells synapse on LGN (Lateral Geniculate Nucleus) neurons
Magnocellular ganglion cells synapse on ventral layers 1 and 2, whereas parvocellular ganglion cells synapse on dorsal layers 3,4,5&6
LGN magno cells extend along dorsal/ parietal “where” pathway
LGN parvo cells extend along ventral/ temporal “what” pathway
Lesions in inferior temporal cortex decrease ability to recognise objects - studied by modelling and electrophysiology

*LGN layers 2,3 and 5 are synapsed on from ipsilateral eye
LGN layers 1,4 and 6 are synapsed on from contralateral eye
60% of synaptic input is from cortex (back propagation)
Many interneurons in the LGN

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19
Q

Receptive fields downstream of V1…

A
  • Increase in complexity of responses of neurons along the ventral stream
  • Increase in the receptive field size of neurons along ventral stream
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20
Q

What are the key features of the cortical structure?

A
  • LAYERING
    Different layers in V1 receive different input and have different properties
  • COLUMNS
  • Ocular columns (input from either ipsilateral or contralateral eye)
    *Tested by Hubel & Weisel - inject radioactive proline in one eye or inject radioactive glucose in cortex and stimulate one eye with light
  • Orientation columns (respond to direction)
  • Blobs (respond to colour)
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21
Q

What is the difference between simple and complex cells in orientation columns?

A

Simple cells are localised in layers 4 and 6 of V1
These respond to a bar in a certain orientation presented in the centre of the receptive field
Simple cell receives input from a large number of lateral geniculate neurons - receptive fields located in a line

Complex cells are localised in layers 2,3 and 5 of V1
These respond to a bar in a certain orientation presented anywhere in the receptive field
Complex cells collect information from many simple cells with similar orientation

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22
Q

What are hypercomplex cells?

A

These are complex cells in orientation columns that stop firing if bar of light in same orientation exceeds receptive field
Firing continues if exceeding bar is in different orientation

23
Q

What are the flaws in the idea that specific neurons in temporal lobe recognise a particular object (e.g. Jennifer Aniston neuron)?

A

X Still poor in scale and orientation invariance
X Do not take into account feedback from higher cortical area (“top-down regulation”)
X Need experimental validation which is difficult, because need to record pre and post synaptic responses

24
Q

What are the areas involved in stimulus localisation and motion processing?

A
  • Retina (orientation selective ganglion cells, motion anticipation)
  • Dorsal parietal “where” stream in the cortex
  • Superior and inferior colliculus

*The superior colliculus receives inputs from ganglion cells, auditory system and somatosensory system
Integrates information from different sensory modalities
and regulates saccadic movements
Deeper layers in SC contain neurons that spike before saccadic movements
These are organised in maps and send projections to layers regulating eye movements
‘Foveation hypothesis’ states interactions between these maps initiates orienting reflex - however this in invalid

25
Q

How is direction selectivity achieved in the retina?

A

Retinal ganglion cells are asymmetric with the preferred direction guessed from morphology
RGCs receives excitatory/ glutaminergic (bipolar) and inhibitory (amacrine) inputs
- In preferred direction, excitation is larger and inhibition is smaller and delayed
- In dull direction, excitation is smaller and delayed and inhibition is larger

*Can use patch clamp technique to determine inputs

26
Q

What is the flash lag illusion?

A

Retina predicts where an object will be
Surrounding cells and NOT the fovea anticipate
If object is moving, spiking rate starts earlier before flash

27
Q

What are the basic strategies used for sound localisation in the VERTICAL plane?

A
  • Monaural Cues (recognize input from one ear)

- Head-related transfer functions (HRTFs) - frequencies altered due to structure of head and ear

28
Q

The basic strategies used for sound localisation in the HORIZONTAL PLANE use binaural cues (inputs from both ears
Describe the Detection of Interaural Level Differences (ILDs)

A

Detection of Interaural Level Differences (ILDs) - the difference in intensities of sound for two ears, as small as 1-dB - mainly for HF sounds

Uses the LSO-MNTB Binaural Excitatory - Inhibitory Pathway

ILDs are encoded by cells in the Lateral Superior Olive (LSO) that compare the coincidence of excitatory
ipsilateral and inhibitory contralateral inputs

The two LSOs act as broad hemispheric channels tuned to sounds mainly from within each hemisphere

The overall position of a sound is encoded by the average output rate of these LSO channels

29
Q

The basic strategies used for sound localisation in the HORIZONTAL PLANE use binaural cues (inputs from both ears
Describe the Detection of Interaural Timing Differences (ITDs)

A

Detection of Interaural Timing Differences (ITDs) - mainly for LF sounds

Uses the Binaural Excitatory-Excitatory Pathway

ITDs are encoded by the MSO cells comparing ipsilateral and contralateral inputs

The two MSOs act as hemispheric channels tuned to sounds from the opposite hemisphere

The overall position of a sound is encoded by the balance between average population response of the two MSO channels

30
Q

Explain how visual prisms affect functional alignment of visual and auditory maps in the midbrain

A

Before prisms ITDs are mapped to frequency specific layers in the ICC (Inferior Colliculus Central)
These frequency layers converge to form a space map in the ICX (Inferior Colliculus Exterior)
The auditory map in the ICX (Inferior Colliculus Exterior) is aligned with the visual map in the optic tectum with instruction from the optic tectum

After prisms, instructions from the optic tectum realigns auditory map in the ICX to match

31
Q

What are the different pools of synaptic vesicles added to plasticity?

A
  • Readily releasable
  • Proximal
  • Reserve/resting
32
Q

What are the advantages of using invertebrates for learning/memory studies?

A

Large neuron size
Low circuit complexity
Temperature dependence allows for mutations
Mapping (developmental, genetics, stereotyped)

33
Q

Habituation is the pairing of an unimportant stimulus to get a reduced response
In Aplysia, continued touching of siphon, leads to habituation by weaker gill withdrawal
Examples of habituation in humans includes:
- eye blink reflex
- repetitive non-harmful stimulus (e.g. live on noisy road)
- visual attention
- emotional response

What is the mechanism of habituation?

A

Depletion of vesicle pool - less neurotransmitter release* - less depolarisation

*50% less

34
Q

Sensitization is when unconditioned stimulus causes increases neuronal firing
What is the mechanism of sensitization?

A

In Aplysia, electric shock stimulates L29 neuron which synapses on before sensory neuron synapses to motor neuron
This causes serotonergic release - serotonin binds to metabotropic
5-HT receptors leading to G protein activation
Activation of adenylate cyclase and cAMP
cAMP activates PKA
PKA phosphorylates and inactivates K+ leading to longer depolarisation

35
Q

Associative learning is the continued neuronal firing upon pairing of conditioned and unconditioned stimulus
What is the mechanism of associated learning?

A

L29 and sensory neuron activate together
Ca2+ influx synergises 5-HT effect from unconditioned stimulus
Ca2+ ions additionally activate adenylate cyclase causing a larger production of cAMP
Gives much longer and stronger action potentials

*These mechanisms have multiple intracellular pathways with varying activation thresholds and long term involve the nucleus

36
Q

What is a Hebbian synapse?

A

“Coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them”

37
Q

What are the key features of the CA3 to CA1 synapse in LTP and LDP?

A

-Shows input specificity
- Show co-operativity
Two pathways converging on the same target can both be strengthened if they fire together

38
Q

What is the mechanism of early and late phase LTP?

A

Activation of NMDAr causes influx of Ca2+
Activation of Ca2+/calmodulin

In early phase LTP, Ca2+/Calmodulin activates CAMKII which auto phosphorylates and phosphorylates AMPAr, enhancing Na+ currents and delivery of ready prepared AMPA receptors to the synapse (AMPAfication)

In late phase LTP, Ca2+/Calmodulin activates adenylate cyclase and cAMP signalling. This activates PKA which phosphorylates CREB-1 and causes transcription of LTP effectors

39
Q

The two types of LTD are:

  • Depotentiation - removal of previous potentiation
  • LTD de novo - no previous potentiation

What are the mechanisms of LTD in the cerebellum

A

In the cerebellum, release of neurotransmitter from the climbing fibre causes activates AMPAr which depolarises cell. Depolarisation activates Ca2+ channels, influx of calcium. Ca2+ activates PKC
Parallel fibre release NT which activates metabotropic glutamate receptors. These activate G protein signalling pathway, PLC which cleaves DAG. DAG activates PKC

PKC phosphorylates AMPA GluR2 subunit (different from LTP)
This reduces currents by internalisation/endocytosis of AMPA receptors

40
Q

The two types of LTD are:

  • Depotentiation - removal of previous potentiation
  • LTD de novo - no previous potentiation

What are the mechanisms of LTD in hippocampus?

A

Occurs at CA3-CA1 synapse

Low frequency stimulus - small increases in Ca2+ from NMDA-r - trigger more phosphatase action and reduce AMPA efficacy

41
Q

What is the role of GAL4/UAS system?

A

Allows the artificial expression of arbitrary transgenes in specific genes
GAL4 binds to UAS - upstream activating system
Only where GAL4DBD and AD are expressed will drive expression of UAS transgene

42
Q

What is the anatomy of the Mushroom Body in Drosophila?

A

Kenyon cells are synapsed on by projection neurons
Kenyon cell axons are subdivided into compartments by innervation of mushroom body output neurons (MBONs)
1:1 matching between output neurons and dopaminergic neuronal axons

43
Q

Kenyon cells have two dopamine receptors

How do dopamine receptors lead to avoidance or approach to a certain odour/shock pairing?

A

If reward/pain then odour/backward pairing, Damb receptor activated, Gq signalling activated, PLC activated releasing IP3 which causes Ca2+ release and leads to forgetting and approach
If punishment/odour then pain/forward pairing, dDA1 receptor activated, Gs signalling activated, adenylate cyclase and cAMP signalling activated. This leads to acquisition and avoidance

*Antagonism between ER Ca2+ vs. cAMP matches forward vs. backward conditions

44
Q

What are the similarities between fly mushroom body and other cerebellum-like structures in other species?

A

Similar to cerebellum in Humans
Input from mossy and climbing fibres to granule cells and output to Purkinje fibres

Similar to electro sensory lobe in weakly electric fish
Input from external electric fields and electric organ to electroreceptors and mossy fibres and then to granule cells- output to Purkinje like cells
Fish needs to learn to ignore signals from its own electric organs so sends efferent copy signal from electric organ to granule cells
Input from mossy fibres and efferent copy at same time are ignored

45
Q

Where is evidence accumulated in primates and Drosophila?

A

In primates, evidence is accumulated in the monkey visual cortex. Lateral intraparietal area responsible for generating saccades
*The stronger the sensory input, the greater the rate of spiking - LIP activity changes faster

In Drosophila, evidence accumulation appears in dendritic integration in Drosophila Kenyon cells

46
Q

What is the role of FoxP channels in evidence accumulation?

A

FoxP suppress K+ channels

K channels are leaky, so suppressed expression by FoxP means slower accumulation

47
Q

r=A/t –> t=A/r

If r has a Gaussian distribution, t has a distribution that only looks Gaussian if

A

x axis scaled to 1/t

48
Q

The mouse pokes its nose in the odour compartment - when it hears a buzz, it has to choose a water part on which odour it smelled . Reward only for going to correct water part
If a mouse’s odour sampling time is cut short by the buzzer, its decisions are …

A

Less accurate

*Moving decision bound adjusts trade off between speed and accuracy

49
Q

What are some mechanisms to activate artificial retina?

A
  • ELECTRICAL STIMULATION
  • LIGHT
  • Channelrhodopsin is a non-selective channel activated by 460nm of light (blue) - opens channel and causes depolarisation
  • Halorhodopsin - stimulated by 570nm (yellow light) - hyperpolarise membrane
  • Small organic compounds e.g. azobenzene
    Quaternary ammonium either activates or inhibits channels - when activated with light - changes isomer structure
    Trans - blocks channel
    Cis - open channel
    Works intracellularly - transported by TRPV1 or P2XR
50
Q

How can you control seizures?

A

Use virus to express channelrhodopsin or halorhodopsin in photoreceptors
Channelrhodopsin depolarises inhibitory cells
Halorhodopsin hyperpolarises excitatory cells

51
Q

What are the benefits of confocal microscopy?

A

Rejects light coming not from focal plane and decreases area of excitation

52
Q

How does fusion of GFP and calcium binding proteins (GcAMP) aid microscopy?

A

GFP is stimulated by blue light and emits green light

In the presence of calcium, these two proteins interact so GFP becomes brighter

53
Q

Patch clamp technique has configurations - on cell, inside out, whole cell and outside out
What are the differences between patch clamp technique and sharp electrodes?

A

Sharp electrodes cannot measure single channels, limited possibility for controlling membrane potential, no solution change inside or outside of cell

Patch clamp technique have limited labelling abilities