Neural Circuitry in the cerebral cortex Flashcards
2 cell types in the cerebral cortex
pyramidal cells - excitatory (glutamate), connections with cortical/subcortical areas, 80%
interneurons - inhibitory (GABA), local, 20%
how do cortical circuits emerge
progenitors
post-mitotic (birth)
axons finding targets
dendrites merge
synapse formation
modification of synaptic connections
layers of the cerebral cortex
neocortex - 6 layers - 90% cerebral hemisphere, sensory/motor
mesocortex - 3-6 layers - majority of the limbic lobe
allocortex - 6 layers - hippocampal formation (archicortex)/primary olfactory areas (paleocortex)
allocortex circuitry
DG is an accumulation of granule cells
DG -> CA3 (mossy fibres)
CA3->CA1 (schaffer collaterals)
entorhinal cortex -> hippocampus (perforant pathway)
what do rodent somatosensory cortex contain
barrels
(whiskers)
inputs of the neocortex
thalamic inputs terminate in layer IV (primary input layer)
layer IV contains special code (ephrins) about axon guidance - tells axons to stay in layer IV
outputs of the neocortex
commissural (cross to other hemisphere) - callosal projections (II, V, VI)
associative (neurons communicate in the same hemisphere) mainly in LII-V
corticofugal (different regions not the cortex): corticothalamic (VI) subcerebral (V): corticotectal, corticobulbar, corticospinal
neuronal diversity
layer II/III - larger pyramidal neurons compared to layer V
interneurons have larger diversity in terms of morphology
neuron types in the cerebral cortex
somatostatin SST (type of martinotti cell) - regular spiking, low threshold spiking
VIP - regular adapting spiking
basket cells (PV+) local , need to buffer Ca2+ (increase metabolic rate/mitochondria) - fast spiking
chandelier cells (PV+/-) contain many terminals for precise control - fast spiking
how do genes make neurons different
different interneurons have different glutamate receptor expression
use RNA seq/single cell seq
transcripts do not always code for a protein
how can we used multimodal data collected from patch clamping interneurons
understand: morphology, electrophysiology, transcriptome MET type 1/2
limitation of MET
not all transcripts express proteins
different axon/soma/dendrites distribution
what are the different cell states
V1
S1
list reasons why 20000 genes specify 10^14 connections
- many proteins from a single gene (splicing isoforms) e.g. neurexins
- many levels from single gene
- multiple proteins from a single protein
- same protein used multiple times
- combinatorial use of proteins
- use of experience/spontaneous neuronal activity via transcription/translation
role of neurexins
pre-synaptic
cell adhesion
slm2 - RNA binding protein (modifies RNA to form different isoforms) WT - 2NRXNB isoform Slm2 KO- longer isoform
what occurs in GluN1 KO
less neural activity
no barrels
CC vs CT pathway
CC pathway - main input from V1-broad selectivity to stimulus orientation
CT pathway - pyramidal neurons tuned to orientation and direction
describe the connectivity of interneurons in the hippocampus
deep layer has more PV interneurons than the superficial layer
gephyrin is the scaffolding for inhibitory synapses
Pyramidal cells with more inhibition project to the amygdala
Pyramidal cells with less inhibition project to the medial entorhinal cortex
what is cell targeting specificity
interneurons connect to dendrites and axons by using Lgi2 in PV interneurons
use syt2 (synaptotagmin) marker - fast spiking
unbalanced excitation/inhibition
hyperexcitation/acute decrease in inhibition - epileptiform
acute decrease in excitation/silent - comatose
cortical inhibition does not prevent epileptiform activity
ratio of e/i is highly dynamic via homeostatic plasticity
feedback inhibition
individual interneurons inhibit >50% principal cells within 100um and receive excitatory inputs from a large portion of them
feedforward inhibition
pyramidal cells and interneurons receive divergent excitatory inputs from different subcortical/cortical regions and layers
failure between excitation and inhibition
neurodegenerative disorders:
ASD
schizophrenia
epilepsy
how do interneurons shape activity of the pyramidal cells
sharpens tuning
if you conduct the pharmacological block of GABAa receptors - this reduces stimulus selectivity in neurons
rodents in darkness vs visual stimuli
GCAMP - ca2+ sensory and is cre dependent
VIP - more activity in darkness
SST/PV - more activity in visual stimuli
different behaviours within the same interneuron
Rat turning L - chocolate Rat turning R - cherry
PV1 - goal run - PV very active
PV2 - goal run - PV not active (more VIP interneurons)
what is the local field potential (LFP)
electrical activity (rhythms/oscillations) close to electrodes used to measure synchronisation
fast oscillations are spontaneous, respond to sensory stimuli, transmission of information
oscillation types
gamma (30-100Hz)
theta (4-8Hz)
multiple gamma oscillations form theta oscillations
optogenetics
channelrhodopsin (cation channel) - membrane depolarisation
halorhodopsin (chloride channel) - membrane hyperpolarisation
how do we know if PV is needed for gamma oscillations
activate PV (express ChR) increase in gamma power at 40x
Sohal et al., 2009 PV silenced - decrease in gamma power
gamma band in humans
adults (18-21) gamma oscillations in facial activity
late adolescents - DA and 5HT still arriving at PFC
high vs low gamma
high gamma = 65-140 Hz
low gamma = 25-50 Hz
what is needed for high gamma oscillations
Yamamoto et al., 2014
if block synaptic transmission using toxin MT between entorhinal cortex and hippocampus - worsen mice performance in free run vs forced turn
optogenetic inhibition of high frequency gamma decreases success rate (use halorhodopsin)
ErbB4 disruption
schizophrenia (altered gamma oscillations)
impaired cognitive function (shown in T maze experiment)
less CCK interneurons - stable gamma oscillations but reduced theta oscillations
control - place cells know coordinates
ErbB4 mutants - no refinement in MWM task
