neuro 206 lecture 2; studying the nervous system

what are neural circuits

organized ensembles of neurons that process specific kinds of information

what are synaptic connections that underlie neural circuits typically made of

neuropil

what are neuropil

the regions between nerve cell bodies where most synaptic connectivity occurs; consists of a dense tangle of dendrites, axon terminals, and glial cell processes

what are the basic constituents of all neurons circuits

afferent neurons, efferent neurons, and interneurons

how do afferent and efferent neurons different

flow of information in neural circuits

afferent neurons

nerve cells that carry info from the periphery TOWARD the BRAIN or spinal cord (Arrive at CNS)

afferent neurons are also known as

sensory neurons

efferent neurons

nerve cells that carry info FROM the BRAIN or spinal cord (Exit CNS)

efferent neurons are also known as

motor neurons

afferent neurons and efferent neurons are collectively referred to as

projection neurons

what are projection neurons known for

their axons extend for a significant distance beyond their cell body and connect with distal targets

what do interneurons do?

participate only in local aspects of circuit function, based on their relatively short axons and the restricted targets with which they connect

interneurons are also known as

local circuit neurons

signals in neural circuits are based on

the chemical neurotransmitter released by receptors in the postsynaptic domain

types of signals neurons can transmit

excitatory signals and inhibitory signals

excitatory signals

enhance electrical activity in the target neuron and make it more likely that the target neuron will relay signals to additional neurons in the circuit via excitatory neurotransmitters

inhibitory neurons

diminish electrical activity in the target neuron far below the threshold necessary for it to transmit electrical signals to additional neurons in the circuit via inhibitory neurotransmitters

modulatory neurotransmitters

modify the thresholds in target neurons, which then changes the effectiveness of either excitatory or inhibitory signals

what is the myotatic reflex also known as

knee-jerk reflex

what are the afferent neurons in the myotatic reflex

sensory neurons with cell bodies in the dorsal root ganglia and send axons peripherally that terminate in sensory endings in the skeletal muscles

what are the targets of the afferent neurons in the myotatic reflex

motor neurons that relay the output activity of the circuit and control the muscles that make the knee jerk

the myotatic reflex circuit has what type of output

divergent

what does having divergent output mean?

there are distinct types of efferent neurons in the circuit

what are the distinct types of efferent motor neurons in the myotatic reflex output circuit?

one type of motor neuron projects to the flexor muscles in the limb, and the other to extensor muscles

what are the functional implications of having divergent output in a neural circuit (myotatic reflex)

flexors and extensors have opposing actions, so there must be one signal that causes the extensor to contract and flexor to relax. there also needs to be interneurons that modulate the input-output signal to turn one of the excitatory inputs into an inhibitory input

the interneurons in the myotatic reflex are…

spinal cord interneurons

summarize the myotatic reflex circuit

• hammer taps, stretches tendon, which stretches sensory receptors in leg extensor muscles

• sensory neuron synapses with and excites motor neuron in the spinal cord; also excites spinal interneuron

• interneuron synapse inhibits motor neuron to flexor muscles

• motor neuron conducts AP to synapses on extensor muscle fibers, causing contraction

• flexor muscle relaxes because the activity of its motor neuron has been inhibited

• leg extends

techniques to study the nervous system

electrophysiological recording

calcium imaging

fMRI

what are the different kinds of electrophysiological recordings?

extracellular recording

intracellular recording

extracellular recording

Electrical activity of neurons can be observed and measured directly via electrodes placed near a neuron to record action potentials

intracellular recording

Electrical activity of neurons can be observed and measured directly via electrodes by accessing the inside of a neuron to record action potentials as well as subthreshold potentials

in terms of the recordings created, how do extracellular and intracellular recordings differ?

extracellular recordings only record action potentials; intracellular recordings record both action potentials and subthreshold potentials

This is an example of what type of recording?

extracellular

This is an example of what type of recording?

intracellular

classical extracellular recording was done with

a single electrode

pros and cons of extracellular recording

high temporal resolution (< 1 ms)

direct measurements of neural activity

invasive

can only measure a few cells at a time

what is temporal resolution?

length of time between distinct measurements

this picture depicts what analytical tool?

multielectrode array

what are multielectrode arrays?

a grid of tightly spaced microscopic electrodes which generally have 1000 sites

what do multielectrode arrays allow for?

enable recoding from 100s to 1000s of cells

what is the main issue with multielectrode arrays?

very invasive

what is the rationale behind using calcium imaging as a tool to study the nervous system

calcium levels inside a cell rise during an AP and gradually return to baseline after the AP; AP causes transient changes in intracellular Ca2+, thus you can measure activity of a cell during different processes based on Ca2+ levels

how does calcium imaging work?

fluorescent calcium indicators (“GCaMP”) enable activity measurement in specific cell types at high spatial resolution.

when Ca2+ binds to calmodulin, creates a conformational change that activates GFP and causes the cell to fluoresce

calcium imaging relies on what kind of measurement?

relative measurement

assess activity by finding the change in fluorescence divided by the baseline level

pros and cons of calcium imaging

high spatial resolution (single cell)

can image multiple cells at once

ok temporal resolution ( > 100 ms)

invasive

limited observation depth (1 mm into tissue)

fMRI stands for…

functional magnetic resonance imaging

what does fMRI do?

measures changes in blood oxygenation related to activity

what is the mechanism behind how fMRI works?

neural activity changes the ratio of oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) in blood (because oxygenated blood goes to active parts of the brain)

oxyHb is diamagnetic but deoxyHb is paramagnetic → radio frequency absorption and emission in a magnetic field changes → effect of emission on magnetic field that we measure changes

pros and cons of fMRI

noninvasive

low temporal resolution

low spatial resolution

fMRI maps show…

the results of a statistical test at each voxel

how are p-values represented chromatically in an fMRI map?

Very low p-values are dark red and progress to blue as it increases, and high p-values remain gray

What do different p-values mean?

low p-values reflect changes likely not due to chance

how do you study a complex system

step 1: observation

step 2: perturbation

step 2a: activate

step 2b: remove

what are ways you can use perturbation to deactivate neurons?

lesions

drugs

optogenetic inhibitors

what is lesion?

removal of brain tissue to assess the causal role of a brain area (if something stops working due to the area being removed, that area is essential for that function)

what are the issues with lesion?

takes long, brain can recover, permanent

how are drugs helpful with studying the brain?

enable faster assessment of functional roles

example of how drugs were used to study nervous system

muscimol (GABA receptor agonist) is injected into the motor cortex to see what role GABA plays in establishing movement and balance by inhibiting GABA’s activity in the system

what are optogenetic inhibitors

can selectively inhibit specific neurons/cellular functions in cells of interest via inserting light-activated ion channels or pumps to hyperpolarize neurons

halorhodopsin

Cl- channel optogenetic inhibitor; lets Cl- into the cell

archaerhodopsin/bacteriorhodopsin

H+ channel optogenetic inhibitor; lets H+ leave the cell

optogenetic inhibitors enable

even faster, genetically-targeted inactivation

what are ways you can use perturbation to activate neurons?

electrical stimulation

channelrhodopsin

how does electrical stimulation allow us to study the brain?

activate neuronal population, so local stimulation activated muscles in different body parts and thus are connected

what are channelrhodopsins?

light-gated ion channels that undergo conformational changes that let cations pass through when hit by light

what can channelrhodopsin be used for?

to rapidly activate genetic subsets of cells