Midterm 1

Neural Circuits

how neurons are organized into ensembles that process specific kinds of information

composed of individual parts (including neurons) connected to perform a specific function

example: myotatic (knee-jerk) reflex circuit

Neuropil

constitutes the regions between nerve cell bodies where most synaptic connectivity occurs

made of the dense tangle of dendrites, axon terminals, and glial cell processes together

Directions that Neurons Carry Information

afferent vs efferent

Afferent Neurons

neurons that carry information from the periphery toward the brain or spinal cord (PNS → CNS)

Efferent Neurons

neurons that carry information from the central nervous system towards the peripheral (CNS → PNS)

Projection Neurons

Afferent and Efferent Neurons

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

Interneurons (AKA Local Circuit Neurons)

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

Excitatory Signals

caused by excitatory neurotransmitters that activate excitatory neurotransmitter receptors and generate signals that 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

causes downstream target cell to be closer to being able to react action potential threshold

Inhibitory Signals

caused by inhibitory neurotransmitters that activate inhibitory neurotransmitter receptors and diminish electrical activity in the target neuron, far below the threshold necessary for it to transmit electrical signals to additional neurons in the circuit

causes downstream target cell to have more difficulting with reaching action potential threshold

Modulatory Neurotransmitters/Neuromodulators

do not enhance target neuron activity nor do they diminish activity below a threshold where signaling is possible; instead modify the thresholds in the target neurons, thus modulating the effectiveness of either excitatory or inhibitory signals

Sensory Neurons

neurons that transform information from the periphery (sensory receptors, etc.) and transmit the signal to the CNS

Motor Neurons

neurons that carry information (via electrical signals) from the CNS to muscles or glands

Myotatic Reflex

knee-jerk reflex circuit, should be able to illustrate/describe how the circuit works:

hammer tap stretches tendon, which in turn, stretches sensory receptors in the leg extensor muscle

sensory afferent neuron transmits signal and synapses with and excites motor neuron in the spinal cord

sensory neuron also excites the spinal neuron that inhibits the motor neuron to the flexor muscles

motor neuron conducts action potential to synapses on extensor muscle fibers, causing contraction

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

leg extends/jerks forward

Electrophysiological Recording

experimental technique that measures the electrical activity of a neuron, categorized as extracellular or intracellular recording

Extracellular recording

electrode is placed near a nerve cell of interest to detect its activity

PROS: helpful for detecting temporal patterns of action potential activity and relating those patterns to stimulation by other inputs or in response to specific behavioral events; less invasive

CONS: cannot be directly used to determine if the cell is being excited/inhibited because the recording cannot differentiate without the subtreshold potentials

Intracellular Recording

electrode is placed inside a cell of interest to detect its activity, done by penetrating the cell or breaking a hole into the cell in some way

PROS: can detect smaller, graded changes in electrical potential that trigger action potentials/subthreshold depolarizations, so better for a more detailed analysis of communication among neurons within a circuit; can be used to determine if the cell is being excited/inhibited; high temporal resolution (can measure <1 ms)

CONS: invasive, can only measure a few cells at a time

Temporal Resolution

length of time between distinct measurements

Receptor/Synaptic Potentials

graded subthreshold triggering potentials that can arise at either sensory receptors or synapses; name is dependent on location!

Calcium Imaging

method of monitoring simultaneous firing activity of multiple cells as long as they ar ein very similar planes

technique/approach that records the transient changes in intracellular concentration of calcium ions that are associated with action potential firing in arrays of individual neurons

because calcium is an important second messenger, calcium imaging can help visualize neuronal activity in large numbers of individual cells by detecting calcium transients in the cytoplasm of multiple cells with relatively high temporal resolution

Optogenetics

technique to manipulate the function of neuronal connections that uses molecular genetic tools that control the activity of specific inputs

Multielectrode Arrays (Extracellular Recording)

has a probe shank with 1000 individual electrodes at each site (think of a checkerboard)

PROS: can record hundreds to thousands of cells at once

CONS: very invasive

Fluorescent Calcium Indicators

enable activity measurement in specific cell types at high spatial resolution

example: GCaMP, which has a binding domain that changes the conformation of the GFP (green fluorescent protein) and causes GFP fluorescence

PROS: high spatial resolution (can see individual cells), can image multiple cells at once, okay temporal resolution (unable to see lots of APs individually)

CONS: invasive, limited observation depth (1 mm into tissue)

Spatial Resolution

how specific size-wise a tool is for measuring activity (higher spatial resolution = can see closer up, such as a single cell)

GCaMP

fusion protein with green fluorescent proten (GFP) and calmodulin subunits, important for calcium imaging

deltaF/F

the change in fluorescence divided by the baseline level (relative measure, not absolute)

fMRI

functional magnetic resonance imaging

measures changes in blood oxygenation related to activity

• activity in brain causes increase in oxygenated blood in that area

• oxygenated blood changes magnetic resonance properties

• fluctuations in magnetic resonance are detected during behaviors

• many trials are averaged to identify brain areas with significantly different levels of activity

• BOLD = Blood Oxygen Level Dependent activity, occurs as neural activity spikes and brain sends more oxygenated blood to that area of the brain

• maps show the results of a statistical test at each voxel, measured in heightened neural activity, NOT total neural activity

• voxel = volume + pixel, and is a region or area, not individual neurons

PROS: noninvasive

CONS: low temporal resolution (averaging), low spatial resolution (2-3 mm), indirectly measures neural activity, so would need a second experiment, such as calcium imaging, to fully visualize activity

Traditional MRI

forms three-dimensional images of brain structure based on the amount of water in structures

works by placing neural tissue in magnetic fields and measuring the emitted signals as hydrogen atoms in water realign

Pertubation

an experimental approach that involves actively disrupting, stimulating, or manipulating neural activity to understand brain function and connectivity

removing tissue to study the effects, in which the lesion can be used to assess the causal role of a brain area

CONS: takes a long time for organism to recover from operation, brain may adapt during healing due to synaptic plasticity, is permanent/non-reversible

alternative: drugs, which enable faster assessments of functional roles that are more tempoerary/reversible

also includes activating neurons, in which local stimulation activates muscles in different body parts

Optogenetic Inhibitors

enable even faster, genetically-targeted inactivation

halorhodopsin responds to yellow light, causes negative Cl- influx to hyperpolarize the cell membrane potential

bacteriorhodopsin responds to orange light, causes positive H+ efflux to hyperpolarize the cell membrane potential

PROS: rapid, precise effect upon light application

Optogenetic Promotor

used to rapidly activate genetic subsets of cells

channelrhodopsin causes inward positive current (Ca2+ and Na2+ influx, small K+ efflux) to depolarize the cell membrane potential

Which technique would be best for measuring a 5 Hz oscillation neuron’s firing rate 4 mm deep into the mouse brain?

Extracellular Recording

Gastrulation (Mammalian Neural Development)

• around days 13-19

• process where a blastocyst (or blastula for non-mammalian organisms) transforms into a gastrula

• embryo transforms from a one dimensional sheet of cells (blastocyst) into a multilayered and three dimensional structure (gastrula)

• begins at the local invagination of cells starting from the primitive pit/node and enlogating to form the primitive streak/groove

• blastocyst elongates and folds into itself

• forms three layers of cells called germ layers (ectoderm, mesoderm, endoderm)

• defines the midline and anterior-posterior and dorsal-ventral axes, establishing the orientation of future development

Germ Layers

layers of the gastrula

outermost is the ectoderm

middle is the mesoderm

innermost is the endoderm