week 5 - experience dependent plasticity Flashcards

Question

What evidence supports that non-activity-dependent factors influence the development of ocular dominance (OD) columns, and what did Crowley and Katz (2000) demonstrate?

Answer 1

: While many studies emphasise the role of neural activity in forming ocular dominance columns, Crowley and Katz (2000) provided compelling evidence that activity-independent mechanisms also contribute to early cortical organisation. Experimental Design: The researchers surgically removed one or both eyes of neonatal ferrets very early in development—before the onset of spontaneous retinal activity or patterned vision. This eliminated any possibility of eye-specific neural activity reaching the brain. They then examined the visual cortex (V1) using anatomical tracing and functional assays during postnatal development. Key Findings: Even in the absence of any retinal input, there were residual patterns of ocular dominance column-like organisation in the visual cortex. Though these patterns were less distinct and more variable than those in normally developing animals, their presence indicated an underlying scaffolding or molecular framework guiding the formation of ocular dominance zones. This contrasts with studies where activity was altered but not removed entirely (e.g., via monocular deprivation), which led to much more dramatic reorganisation. Conclusion: Crowley and Katz demonstrated that molecular cues or intrinsic developmental programs—such as axon guidance molecules and genetic patterning—can initiate the early layout of cortical structures like OD columns. However, full refinement and maintenance of these structures still depend on neural activity. This study emphasizes that both activity-dependent and activity-independent mechanisms are required for proper sensory map development.

Answer 2

: Hebbian plasticity drives the formation of OD columns before visual experience begins by acting on spontaneous, uncorrelated retinal activity from each eye. Mechanism: Before eye opening, retinal ganglion cells spontaneously fire in uncorrelated bursts, with left and right eyes generating distinct activity patterns. These patterns reach the lateral geniculate nucleus (LGN) and then the primary visual cortex (V1), where inputs from both eyes initially overlap. Hebbian plasticity then operates on these signals: Inputs that fire together (i.e., from the same eye) are strengthened. Inputs that fire out of sync (i.e., from the opposite eye) are weakened. Over time, this activity-dependent synaptic modification segregates left and right eye inputs into alternating columns in Layer 4 of V1—forming the ocular dominance map. Summary: This is a classic example of "fire together, wire together"—Hebbian rules applied to spontaneous activity can organise neural circuits even in the absence of sensory input.

Answer 3

Kleinschmidt, Bear, and Singer (1987) showed that blocking NMDA receptors in V1 prevents ocular dominance shifts during monocular deprivation (MD). Experiment: Animals underwent monocular deprivation during the critical period. In some animals, NMDA receptor activity in V1 was blocked using pharmacological agents. In these animals, no shift in ocular dominance occurred, despite the deprivation. Conclusion: NMDA receptors are critical for LTP/LTD mechanisms that underlie Hebbian plasticity. Without NMDA-mediated calcium influx, synapses from the deprived eye do not weaken, and dominance does not shift. This confirms that ocular dominance plasticity is NMDA-dependent, reinforcing Hebbian mechanisms.

Answer 4

A: GABAergic inhibition regulates the timing of the critical period, the window of heightened plasticity in postnatal development. Key Studies: Kirkwood and Bear (1994) showed that feed-forward inhibition is needed to open and later close the critical period. Hensch and Maffei groups demonstrated that: Low inhibition = immature circuit, too noisy for precise Hebbian plasticity. Moderate inhibition = opens the critical period by stabilising circuits and lowering noise. High inhibition = closes the critical period by suppressing activity below the plasticity threshold. Conclusion: The level of cortical inhibition gates when Hebbian plasticity can occur. This determines when the brain is most sensitive to experience and when that sensitivity ends.

Answer 5

Orientation selectivity refers to the tendency of V1 neurons to respond preferentially to edges of a specific angle. Key Findings: Hubel and Wiesel (1968) first described orientation-selective cells in V1. Bear et al. (1990) used APV (an NMDA receptor antagonist) to block NMDA receptors in developing animals: Result: Orientation tuning failed to develop, showing that NMDA receptor activity is essential for the experience-driven refinement of these properties. Mechanism: Orientation selectivity is sharpened via Hebbian strengthening of inputs aligned with preferred orientations. Requires visual input during development and NMDA receptor activation. Conclusion: Orientation selectivity develops through experience-dependent synaptic plasticity, requiring both sensory input and NMDA-mediated Hebbian mechanisms.

Answer 6

Associative learning refines sensory representations by modifying the strength and selectivity of neuronal responses to stimuli. Key Experiments: Schoups et al. (2001): Trained monkeys on orientation discrimination tasks. Found increased tuning sharpness in V1 neurons—steeper tuning curves for trained orientations. Poort et al. (2022): Used two-photon calcium imaging in awake, behaving mice during visual discrimination learning. Found suppression of responses to non-preferred stimuli, enhancing contrast between representations. Khan & Hofer (2018): Showed that inhibitory microcircuits gate plasticity during associative learning, determining when learning-induced changes can occur. Conclusion: Associative learning improves neuronal discrimination by refining orientation tuning—either by enhancing preferred responses or suppressing non-preferred ones. This process is experience-dependent, task-specific, and gated by local inhibition.

Answer 7

Critical periods occur at different times for different regions of the brain, with primary sensory regions of neocortex passing through a critical period earlier than higher order regions. * The opening of the critical period is determined by an increase in cortical inhibition that reduces noise and allows experience to drive Hebbian plasticity. * The closure of the critical period is determined by a further increase in cortical inhibition which prevents sensory experience from driving enough activity for Hebbian plasticity to occur. * The likelihood of plasticity occurring, and its direction can be governed not only by GABAergic inhibition but also other molecular factors such as NMDA receptor composition. * Aberrant sensation during critical periods of post-natal development can result in lasting sensory conditions, such as amblyopia. * Pharmaceutical agents, such as fluoxetine, have been used to reopen the critical period, while other interventions, including sensory deprivation appear to have a similar effect

Answer 8

Calcium imaging is a method to monitor neuronal activity by detecting calcium ion (Ca²⁺) influx, which occurs during action potentials. GCaMP: A Genetically Encoded Calcium Sensor GCaMP combines: GFP (Green Fluorescent Protein) – derived from Aequorea victoria jellyfish Calmodulin (CaM) – a calcium-binding protein RS20 peptide – binds to calmodulin when calcium is present How It Works: When a neuron fires, Ca²⁺ enters the cell. Ca²⁺ binds to calmodulin, changing its conformation. This brings GFP into a fluorescent state, emitting green light. The fluorescence intensity increases with neural activity, allowing real-time visualisation of spiking. Experimental Setup (Chen et al., 2013; Rupprecht et al., 2021): A patch pipette or viral vector introduces GCaMP into neurons. An objective lens captures the fluorescence signal across an imaging plane. Neural activity is recorded as changes in fluorescence, often aligned with spike events. Conclusion: GCaMP-based calcium imaging is a powerful, non-invasive tool for tracking population-level or single-cell neural dynamics in vivo, especially during behaviour or learning.

Answer 9

Hebbian plasticity accounts for ocular dominance column formation in Layer 4 of V1 through spontaneous retinal activity before eye opening. Uncorrelated activity from each eye strengthens intra-eye synapses and weakens inter-eye competition, leading to segregation into alternating eye-specific columns.

Answer 10

Monocular deprivation reduces activity from the deprived eye. Under Hebbian rules ("use it or lose it"), weakened input leads to LTD-like synaptic depression, while the non-deprived eye strengthens via LTP. This causes a shift in ocular dominance towards the open eye.

Answer 11

Experience-driven activation of neurons by specific edge orientations leads to synaptic strengthening for co-active inputs (Hebb’s rule). Over time, this results in neurons becoming selectively tuned to particular orientations, refining cortical feature maps in V1.

Answer 12

Associative learning refines neural coding by enhancing responses to relevant stimuli and suppressing irrelevant ones. This results in improved tuning, sharper representations, and better discrimination, especially in sensory cortices like V1 (e.g. Poort et al., 2022; Schoups et al., 2001).

Answer 13

GABAergic inhibition regulates the onset and closure of critical periods: Moderate inhibition reduces network noise, allowing Hebbian plasticity. Excessive inhibition suppresses activity, closing the window for plasticity. This gates when experience can shape circuits.

Answer 14

In adulthood, local inhibitory circuits modulate when and where plasticity occurs. This top-down gating, shown in studies like Khan & Hofer (2018), allows plasticity to be task-relevant and context-sensitive, ensuring learning occurs only under appropriate conditions.