Development Circuits

What does the 'whisker barrel' pattern represent in mice?

Each whisker on the contralateral face maps to a specific 'barrel' in layer 4 of the somatosensory cortex (S1).

Where are 'barrels', 'barrelloids', and 'barrelettes' located?

Barrels → cortex (layer 4);

Barrelloids → thalamus (VPM);

Barrelettes → brainstem.

What happens if whisker follicles are lesioned before P4?

The corresponding cortical barrel fails to form - P4 marks the end of the critical period for barrel formation.

What does VGlut2 knockout (KO) show about barrel formation?

Without VGlut2 (no glutamate release), barrels fail to form -  proving synaptic transmission from thalamus to cortex is essential.

What happens in Munc18 KO mice?

Blocking vesicle fusion disrupts axon branching and prevents Layer 4 cells from adopting their normal stellate morphology.

What is the role of subplate (SP) neurons in early cortical development?

They act as a temporary relay, guiding thalamocortical (TC) axons to their final target (Layer 4).

At what stage do TC axons first reach the cortex and layer 4?

They form early contacts with SP neurons around E15 and reach layer 4 by P8.

What happens in Reeler mice (no Reelin)?

SP neurons end up misplaced in layer 1, but TC axons still connect to L4 later - showing guidance mechanisms are robust.

What happens in Gli3 mutant mice?

Subplate neurons fail to develop → corticothalamic axons don’t form, and TC axons stop prematurely → disrupted sensory circuit formation.

Why are transient circuits important during early development?

Early TC-SST+ interneuron connections and SST-PV connections shape proper feedforward inhibition; if disrupted, permanent network alterations occur.

Define a 'critical period.'

A developmental window when specific stimuli are required for normal circuit maturation; absence causes irreversible changes.

What is ocular dominance plasticity (ODP)?

The shift in visual cortical responsiveness after monocular deprivation - neurons become more responsive to the open eye.

When is the critical period for ODP in mice?

Roughly P21-P35, peaking around P28.

What is the role of GABAergic inhibition in opening the critical period?

Sufficient GABA activity (from PV+ interneurons) is necessary to trigger plasticity onset.

What happens in GAD65 KO mice?

Weak inhibition → no ODP after monocular deprivation (no shift).

How can diazepam restore plasticity in GAD65 KO mice?

It enhances GABA signaling, rescuing ODP - proving inhibition 'opens' the critical period.

What happens if diazepam is injected before the normal critical period?

It induces early ODP - showing GABA maturation sets the timing of the critical period.

What is BDNF’s role in critical period timing?

BDNF promotes maturation of PV+ interneurons and accelerates GABAergic circuit development.

What happens when BDNF expression is accelerated?

The critical period opens and closes earlier, reducing later plasticity.

What is Otx2 and how does it affect the visual cortex?

A transcription factor made in the retina; transported to V1 after eye-opening; promotes PV+ interneuron and PNN maturation.

What happens if Otx2 transport is blocked (e.g., with an antibody in the retina)?

PV+ interneurons and PNNs stay immature → no ocular dominance plasticity.

What are perineuronal nets (PNNs)?

Extracellular matrix structures around PV+ interneurons that stabilize circuits and close the critical period.

What are twitches?

Brief, jerky, coordinated movements during active (REM-like) sleep, occurring against background muscle atonia.

Why are twitches important in early development?

They drive sensory feedback that helps the brain map the body and coordinate sensorimotor circuits.

When do cortical responses to twitches peak?

Before P12, motor cortex responds more to twitches than to wake movements.

What happens between P8 and P12 in motor cortex responses?

A developmental shift - awake movements begin to dominate, showing maturation of voluntary control.

How do twitches coordinate large-scale brain activity?

They synchronize somatosensory, hippocampal, and motor regions - helping establish long-range connectivity.

What brain areas relay twitch-related signals?

Red nucleus → spinal cord → hippocampus/entorhinal cortex (via thalamic gating).

Why is the developing brain not a small adult brain?

It has unique physiological properties - transient neurons, circuits, and heightened plasticity - crucial for network formation.

How are the whisker barrel system and ocular dominance system similar conceptually?

Both depend on sensory-driven refinement within a critical period and on activity-dependent synaptic signaling.

What happens if you inject anti-Otx2 at P26 and perform monocular deprivation until P30?

The deprived eye won’t lose dominance because Otx2 can’t reach V1 → PV+ interneurons stay immature → no ODP shift.