Developmental plasticity

Annotations:

• / Experience dependent

1. Local circuit models of critical period plasticity
   1. 'instructive' model
   2. 'permissive' model
2. Critical periods

   Annotations:

   • defined period within early postnatal development with a heightened or exclusive capacity for plasticity

   Attachments:

   • Critical periods and local circuits
   1. Pathology
      1. cleft palate and speech
      2. amblyopia / lazy eye
   2. local circuits
3. Cortical plasticity
   1. Sensory

      Attachments:

      • Developmental plasticity
      1. Ocular dominance plasticity (V1)
         1. Hubel & Weisel (1962)- monocular deprivation
            1. during critical period (19–32 days of age)

               Annotations:

               • causes a rapid loss of responses to the deprived eye, followed by a slower gain of responses to the open eye, leading to a physiological shift in ocular dominance
               1. shift of response potentiation from deprived eye to the other, response depression to the deprived eye
         2. Rodents- lack discrete ocular dominance columns

            Annotations:

            •    ·         Rodent V1 lacks discrete ocular dominance columns but has a small binocular region in which individual neurons exhibit visual responses to both eyes.   
         3. Where?
            1. L4
            2. L2/3
               1. early locus for plasticity

                  Annotations:

                  • plasticity can occur in L2/3 before in L4
         4. Adult vs neonatal

            Annotations:

            • Ocular dominance plasticity persists in adult rodents but is slower and mediated mostly by response potentiation, like map plasticity in S1. In contrast, adult cats and primates show substantially less adult plasticity.   
            1. Adult- slower, mostly response potentationa
      2. Barrel cortex (S1)
         1. neonates (<2-6 days)

            Annotations:

            • Plasticity occurs at multiple sites and layers in S1, with L4 being a primary site of plasticity in neonates (&lt;4–6 days of age), 
            1. response depression and potentiation
         2. adults

            Annotations:

            • in juveniles and adults, plasticity occurs most rapidly and extensively, and sometimes exclusively, in L2/3 
            1. only response potentiation

               Annotations:

               • limited plasticity
         3. Net effect- rewiring connections for optimal sensory processing

            Annotations:

            •    ·         The net effect of this map plasticity is to dynamically reallocate cortical processing space from deprived inputs toward spared inputs, which may optimize sensory processing. For detailed review of S1 map plasticity, see Feldman &amp; Brecht (2005) and Fox (2002).   
         4. Whisker deprivation
            1. Deprivation studies:
               1. Hebbian
                  1. All but 1 (D1) whisker
                     1. increased receptive field of that whisker

                        Annotations:

                        • the receptive field grows to try to compensate to the loss in sensory input, however the resolution would decrease massively
                  2. All but D1 and D2
                     1. The receptive fields combine/ overlap
               2. Non-hebbian
                  1. Overstimulation of D1
                     1. only D1 decreased receptive field
                  2. Enriched environment
                     1. All decrease receptive field
         5. whisker stimulation
            1. AMPA (GluR1) insertion

               Annotations:

               •    ·         whisker stimulation at P12–14 in rats drives a recombinant AMPA receptor subunit (GluR1) into synapses from layers 4 to 2/3 in the somatosensory barrel cortex92.   
               1. Expression of the GluR1 cytoplasmic tail

                  Annotations:

                  • which inhibits the synaptic delivery of endogenous receptors during LTP in vitro, blocks this insertion and subsequent synaptic potentiation in vivo.   
      3. Five Common Components

         Annotations:

         • 1-2: These components of plasticity are classically hypothesized to involve Hebbian weakening and strengthening of deprived and spared pathways, and to be driven by competition between active and inactive inputs, because less or no plasticity occurs when all inputs are deprived (Wiesel &amp; Hubel 1965). Response potentiation must involve a competitive process because it is driven heterosynaptically by depriving neighboring inputs. (On the cellular level, this could be accomplished by classical heterosynaptic plasticity or by homeostatic plasticity or metaplasticity affecting all synapses on a neuron.) Whether response depression is a competitive process is less clear. In some cases, response depression requires neighboring, active inputs (Glazewski et al. 1998), which may heterosynaptically depress deprived inputs. However, response depression can also occur when all inputs are deprived (Wallace &amp; Fox 1999, Kaneko et al. 2008b), which is more consistent with noncompetitive, homosynaptic plasticity driven by residual activity on deprived pathways (Rittenhouse et al. 1999, Frenkel &amp; Bear 2004).   
         • 3-4: The third and fourth components are both consistent with Hebbian strengthening of active inputs but differ in dependence on attention or reward. These are driven homosynaptically or cooperatively by activity on active pathways and therefore appear functionally distinct from potentiation of spared inputs during deprivation-induced plasticity
         1. 1. rapid response depression to deprived inputs
            1. Hebbian
            2. physiological- NMDA-LTD/ CB1-LTD
            3. Structural- Slow- macroscopic changes in axonal projections
         2. 2. response potentiation to spared inputs, when a subset of inputs are deprived.
            1. Physiological- NMDA-LTP/ NO-LTP
            2. Structural- Rapid changes in synaptic spikes
         3. 3. use- and correlation dependent potentiation
            1. Hebbian
            2. Physiological- NMDA-LTP; STDP
         4. 4.Training-dependnet potentiation in adults
            1. Hebbian
         5. 5. substantial overuse or deprivation
            1. Physiological- homeostatic/ metaplasticity
            2. Structural- inhibitory synaptogensis
      4. Auditory cortex (A1)
      5. response depression

         Annotations:

         • Depression of responses to deprived whiskers/eye (termed response depression)  have distinct dynamics, are separable developmentally and genetically, and can be differentially induced by different patterns of whisker deprivation. They therefore represent distinct functional components and mechanisms of plasticity 
      6. response potentiation

         Annotations:

         • potentiation of responses to spared whiskers/eye (response potentiation)
      7. response potentiation and depression- separate mechanisms

         Annotations:

         • have distinct dynamics, are separable developmentally and genetically, and can be differentially induced by different patterns of whisker deprivation. They therefore represent distinct functional components and mechanisms of plasticity 
   2. Mechanisms
      1. Structural

         Annotations:

         • physical rewiring of cortical circuits by synapse formation, elimination, and morphological change
         1. Rapid- (hours to days)

            Annotations:

            • occur continuously at the level of spines and synapses
            1. experience dependent
               1. whisker and visual deprivation
                  1. reduced dendritic spines

                     Annotations:

                     • dendritic spines of L5 and L2/3 cortical pyramidal cells appear, disappear, and change shape in hours-days
               2. dendritic spine formantion/ retraction- associated with synapse formation and elimination
                  1. young vs adult

                     Annotations:

                     • Spines are more dynamic in young adult mice (1–2 months) than in mature mice (4–5 months) 
                  2. S1 vs V1

                     Annotations:

                     • more dynamic in mature S1 than in V1
               3. brief monocular deprivation
                  1. increases spine dynamics and alters spine number in binocular V1

                     Annotations:

                     • consistent with formation of excitatory synapses to mediate potentiation of open-eye responses 
         2. relation of physiological plasticity?

            Annotations:

            • A major unanswered question is how these synapse-scale structural changes relate to physiological plasticity of synapses and to macroscopic structural changes in axonal projections
            1. direct evidence lacking
               1. structural modification- LTP/LTD linked- during experience-dependent plasticity?

                  Annotations:

                  • However, whether structural modification is linked to LTP and LTD during experience-dependent cortical plasticity or is independent remains unknown
            2. indirect evidence
               1. rapid spine plasticity - by product of LTP, LTD

                  Annotations:

                  • Because spine plasticity can accompany experimentally induced LTP and LTD (Alvarez &amp; Sabatini 2007), one model proposes that activity rapidly regulates existing synapse strength via LTP and LTD, leading to formation and removal of spines and synapses that effectively rewire cortical microcircuits
                  1. leads to slow macroscopic changes in axons and dendrites

                     Annotations:

                     • In turn, this rewiring may lead to slower, macroscopic changes in axons and dendrites (Cline &amp; Haas 2008). 
         3. slow- day-weeks
            1. Slow, Large scale changes- Axonal projections

               Annotations:

               • including thalamocortical and horizontal, cross-columnar axons and, to a lesser extent, dendrites 
               1. whisker deprivation- reduces L2/3 projections, input

                  Annotations:

                  • whisker deprivation reduces L2/3 horizontal axonal projections extending toward deprived columns (Broser et al. 2007), and reduces L2/3 input from L4 barrels versus interbarrel septa (Shepherd et al. 2003). 
               2. Slow- lag physiologically measured plasticity by several days or weeks
      2. Physiological

         Annotations:

         • functional modification of existing synapses and neurons
         1. Homeostatic Plasticity

            Annotations:

            •    Refers to mechanisms that try to compensate/restore to the change of sensory inputs to a ‘set point’   
            •    ·         Turrigiano &amp; Nelson (2004) propose that such homeostatic plasticity stabilizes mean cortical activity in the face of slowly changing input levels and in response to synaptogenesis and synapse elimination during development (Turrigiano &amp; Nelson 2004).   
            • This homeostatic plasticity was discovered in cortical cultures in vitro, where experimentally increasing (or decreasing) network activity over hours to days causes a uniform, multiplicative decrease (or increase) in excitatory synapse strength, termed homeostatic synaptic scaling. 
            1. S1- whisker deflection (overstimulation)

               Annotations:

               • 24 hours of continuous whisker deflection weakens the S1 representation of the stimulated whisker
               1. decreases representations
            2. V1
               1. V1- visual deprivation

                  Annotations:

                  • visual deprivation increases visual responses in the deprived monocular zone of rodent V1 (Knott et al. 2002, Mrsic-Flogel et al. 2007). 
                  1. increases responses
               2. monocular closure in binocular visual cortex

                  Annotations:

                  •    ·         Homeostatic plasticity also occurs during more modest sensory manipulations, such as monocular closure in binocular visual cortex, and thus is likely to contribute to multiple types of cortical plasticity (Mrsic-Flogel et al. 2007, Maffei &amp; Turrigiano 2008).   
         2. LTP
            1. young
               1. mediates use-correlation dependent plasticity

                  Annotations:

                  • LTP has been proposed to underlie use-dependent and temporal correlation-dependent strengthening of sensory responses 
            2. adult
               1. strengthening of responses/ spared inputs- reinforcement/ deprivation

                  Annotations:

                  • reinforcement-dependent strengthening of responses in adults, and strengthening of spared inputs during deprivation-induced plasticity. Many neocortical excitatory synapses exhibit LTP 
            3. strengthening of sensory responses
            4. postsynaptic
               1. NMDA-LTP in the neocortex
                  1. S1-L4-L2/3 synapse

                     Annotations:

                     • normal whisker experience strengthens developing L4-L2/3 synapses by GluR1 insertion, which likely represents NMDA-LTP 
                     1. use-correlation depedennt -whisker experience
                        1. GluR1 insertion
                           1. Viral expression of GluR1 - increase response

                              Annotations:

                              • Viral expression of GluR1 in developing L2/3 neurons in vivo causes increased rectification at L4-L2/3 synapses
                           2. viral transfection of GluR1-ct

                              Annotations:

                              • which prevents GluR1 insertion, doesn't show an increase in response
                        2. whisker experience - increase in response

                           Annotations:

                           • whisker experience strengthens developing L4-L2/3 excitatory synapses via NMDA-LTP, as shown by molecular interventions that alter AMPA receptor trafficking
                        3. whisker trimming- no increase in response
                     2. spared input enhancement- deprivation
                        1. knockout mice

                           Annotations:

                           • show that α/δ CREB, α-CaMKII, and α-CaMKII autophosphorylation are all required for response potentiation in L2/3 in vivo, consistent with a requirement for NMDA-LTP (Glazewski et al. 1996, 1999, 2000). 
                           1. CREB
                           2. CaMKII
                        2. deprivation of all but 1 whisker

                           Annotations:

                           • which drives response potentiation to the spared whisker in L2/3 of the spared column
                           1. increases quantal size, AMPA:NMDA ratio, and AMPA current rectification
                           2. blocked by GluR1 knockout
                           3. completely blocked by combined GluR1 and neuronal nitric oxide synthase (nNOS) knockout

                              Annotations:

                              •    both NMDA-LTP and presynaptic, NO-dependent LTP are involved in response potentiation (Fox et al. 2007).   
                  2. mouse V1
                     1. high-contrast grating stimuli
                        1. increased response blocked by NMDA anta/ viral expression of GluR1-ct
            5. presynaptic
               1. increase Pr
               2. NO- retrograde messenger in L4-L2/3 synapse
                  1. single whisker exp- completely blocked by combined GluR1 and neuronal nitric oxide synthase (nNOS) knockout
         3. LTD

            Annotations:

            • LTD implements use-dependent, homosynaptic and heterosynaptic weakening and therefore may mediate response depression to deprived inputs. 
            1. NMDA LTD

               Annotations:

               • calcium from postsynaptic NMDA receptors activates protein phosphatases including calcineurin, leading to dephosphorylation of specific sites on the AMPA receptor GluR1 subunit and internalization of synaptic AMPA receptors
               1. Cortex

                  Annotations:

                  • In cortex, NMDA-LTD (defined by NMDA receptor involvement and AMPA receptor internalization) has been clearly observed at thalamocortical synapses in V1, and likely S1 (Feldman et al. 1998, Crozier et al. 2007), and at other synapses in sensory, anterior cingulate, entorhinal, and perirhinal cortex (Dodt et al. 1999, Toyoda et al. 2006, Deng &amp; Lei 2007, Griffiths et al. 2008). 
                  1. S1
                     1. whisker deprivation

                        Annotations:

                        • occludes the induction of NMDA-LTD by LFS-   which supports the idea that the mechanisms mediating changes in barrel cortex responsiveness are the same as those that mediate LTD.  
                  2. anterior cingulate
                  3. PRH
                     1. non-depreivation mediated
                        1. visual experience

                           Annotations:

                           • visual experience weakens responses to familiar visual stimuli, a phenomenon that may contribute to visual recognition memory. 
                        2. blocking AMPAR internalisation

                           Annotations:

                           •    NMDA-LTD is prominent in adult perirhinal cortex, and peptides that block AMPA receptor internalization block both LTD and visual recognition memory (Griffiths et al. 2008).   
                  4. Ent
                  5. V1- Monocular deprivation
                     1. reduces AMPAR surface expression, phospho

                        Annotations:

                        • Monocular deprivation decreases AMPAR surface expression and alters GluR1 phosphorylation similar to NMDA-LTD (Heynen et al. 2003). 
                     2. L4
                     3. reduces the saturation level of LTD in response to repeated LFS
               2. L4 synapses

                  Annotations:

                  • L4 synapses exhibit NMDA-LTD (Crozier et al. 2007). 
            2. mGluR-LTD
               1. Not involved
                  1. mGluR2 KO- no affect

                     Annotations:

                     •    mGluR2-dependent LTD is not likely to be involved because mGluR2 knockout does not disrupt ocular dominance plasticity (Renger et al. 2002).   
            3. CB1-LTD
               1. retrograde - presynaptic LTD

                  Annotations:

                  • postsynaptic calcium elevation and activation of group I mGluRs drive postsynaptic endocannabinoid synthesis, which signals retrogradely to presynaptic CB1 receptors, driving a long-lasting decrease in release probability 
               2. neocortical excitatory synapses

                  Annotations:

                  • CB1-LTD occurs at many neocortical excitatory synapses 
               3. postsynaptic NMDA-independent, presynaptic NMDA-dependent

                  Annotations:

                  •    CB1-LTD is independent of postsynaptic NMDA receptors but may require presynaptic NMDA receptors, which exist at specific neocortical synapses (Sjostrom et al. 2003, Rodriguez-Moreno &amp; Paulsen 2008).   
               4. S1-whisker deprevation

                  Annotations:

                  • These findings suggest that deprivation weakens L4–L2/3 synapses in vivo by CB1-LTD. 
                  1. response deprivation at L4-L2/3

                     Annotations:

                     • response depression to deprived whiskers primarily in L2/3, not L4, suggesting LTD at L4–L2/3 excitatory synapses (Glazewski &amp; Fox 1996, Drew &amp; Feldman 2009). 
                     1. ex vivo S1 slices
                  2. presynaptic
                     1. PPD to PPF

                        Annotations:

                        • Deprivation converts normal paired pulse depression into facilitation and slows use-dependent blockade of NMDA-EPSCs by MK-801, indicating a decrease in release probability at these synapses (Bender et al. 2006a). 
                        1. decreased release Pr
                     2. no posynaptic changes

                        Annotations:

                        • In contrast, neither postsynaptic excitability (Allen et al. 2003) nor measures of postsynaptic responsiveness (mEPSC amplitude, quantal L4–L2/3 synaptic currents, AMPA:NMDA ratio) are altered (Bender et al. 2006a). 
                  3. occludes CB1-LTD

                     Annotations:

                     • Deprivation-induced synapse weakening occludes CB1-LTD, which is prominent at L4–L2/3 synapses and which is also expressed as a decrease in presynaptic release probability (Allen et al. 2003, Bender et al. 2006b). 
                  4. CB1 antagonist

                     Annotations:

                     •    systemic injection of a CB1 antagonist prevents rapid deprivation-induced weakening of L4–L2/3 synapses and prevents depression of responses to deprived whiskers (Li et al. 2007).   
                  5. structural
                     1. reduces L2/3 projections, input

                        Annotations:

                        • whisker deprivation reduces L2/3 horizontal axonal projections extending toward deprived columns (Broser et al. 2007), and reduces L2/3 input from L4 barrels versus interbarrel septa (Shepherd et al. 2003). 
               5. L2/3

                  Annotations:

                  • L4–L2/3 synapses exhibit CB1-LTD in vitro
               6. V1- monocular deprivation
                  1. CB1 receptor anta- blocks L2/3 LTD

                     Annotations:

                     • Systemic pharmacological blockade of CB1 receptors in vivo prevents depression of closed-eye responses in L2/3, but not in L4, suggesting that CB1-LTD is a critical mechanism for response depression in L2/3, whereas other mechanisms, potentially including NMDA-LTD, are active in L4 (Liu et al. 2008). 
            4. Age

               Annotations:

               • In young animals (&lt;2 months) whisker and visual deprivation drive both response depression and response potentiation in V1 and S1, whereas in adults, response potentiation occurs solely or primarily (Sawtell et al. 2003, Fox &amp; Wong 2005, Sato &amp; Stryker 2008). 
               1. young animals (<2 months)
                  1. deprivation-mediated

                     Annotations:

                     • deprivation may drive LTD primarily in young animals, contributing to the more rapid and extensive plasticity at young ages. 
                     1. NMDA/CB1-LTD
               2. Adult
                  1. non-deprivation mediated
                     1. NMDA-LTD
            5. in ocular dominance plasticity

               Annotations:

               • Despite this strong evidence for LTD in ocular dominance plasticity, several manipulations that block LTD in vitro, including knockout of PKA RIβ and transgenic overexpression of BDNF, do not block ocular dominance plasticity (Hanover et al. 1999, Hensch 2005). 
         4. Spike timing-dependent
            1. mechanisms

               Annotations:

               • the mechanisms of STDP is different at different synapses 
               1. NMDA=LTP/ LTD
               2. NMDA-LTP and CB1-LTD
            2. Neocortex- in-vivo/vitro

               Annotations:

               • STDP occurs at many neocortical synapses in vitro and can be induced experimentally in vivo by pairing sensory stimulation with precisely timed spikes (Meliza &amp; Dan 2006, Jacob et al. 2007). 
            3. use-correlation depedennt
               1. perceptual learning- V1

                  Annotations:

                  • Thus, STDP drives perceptual learning in V1 in response to appropriate timed visual stimuli. 
                  1. brief visual stimuli at two nearby retinotopic locations

                     Annotations:

                     • imposes specific spike timing on V1 neurons representing these locations
                     1. repeated stimuli- adult cats

                        Annotations:

                        • alters the functional strength of synaptic connections between activated neurons and spatially shifts neuronal receptive fields in a manner consistent with STDP
                     2. humans

                        Annotations:

                        • the same conditioning procedure causes a shift in the perceived location of visual stimuli, again consistent with STDP (Fu et al. 2002). 
               2. A1

                  Annotations:

                  • similar  conditioning procedure shifts frequency tuning of A1 neurons consistent with STDP (Dahmen et al. 2008). 
            4. deprivation- dependent
               1. S1 - L4-L2/3

                  Annotations:

                  • STDP may also drive LTD at L4-L2/3 synapses in response to sensory deprivation. L4-L2/3 synapses in S1 exhibit robust STDP in vitro (Feldman 2000, Nevian &amp; Sakmann 2006) and undergo LTD in vivo in response to whisker deprivation 
         5. Metaplasticity

            Annotations:

            • In metaplasticity, experience-dependent alterations in inhibitory tone, dendritic excitability, NMDA receptor function, or neuromodulation alter the ability of future stimuli to drive LTP and LTD. 
            1. V1

               Annotations:

               • visual experience regulates the capacity for LTP and LTD at L4-L2/3 synapses by regulating NMDA receptor subunit composition 
               1. regulation NMDAR subunit composition
               2. homeostatic

                  Annotations:

                  • This form of metaplasticity is homeostatic: Visual deprivation biases LTP/LTD learning rules toward LTP so that subsequent activity tends to strengthen synapses and restore mean cortical activity
               3. monocular deprivation

                  Annotations:

                  • Such metaplasticity was hypothesized to counteract the inherently unstable, positive-feedback nature of Hebbian synaptic plasticity and may act during monocular deprivation to promote LTP by open-eye inputs, thereby driving response potentiation 
            2. S1
               1. single whisker experience
                  1. induces mGluR-LTP

                     Annotations:

                     •    In S1, single whisker experience both drives NMDA-LTP at L4-L2/3 synapses and induces a form of metaplasticity in which a novel mGluR-LTP appears. This mGluR-LTP is required after initial potentiation to maintain synapse strength in vivo (Clem et al. 2008).   
   3. Types
      1. Diseased-Deprivation- Response potentiation and depression
      2. Normal- No deprivation- Use-Correlation-Dependent Plasticity

         Annotations:

         • repeated activation of a specific sensory input (without deprivation) potentiates neural responses to that input. This is usually most robust in young animals
         1. repeated stimulation
         2. Learning-Related Plasticity in Adults

            Annotations:

            • Learning in adults is more limited and slower, but can occur when stimuli are behaviourally relevant 
            1. reinforcement / classical conditioning
               1. A1- increased responses to trained frequencies

                  Annotations:

                  •    ·         classical conditioning using tone stimuli increases A1 responses to trained frequencies (Weinberger 2007),   
               2. S1-increased representations of trained stimuli

                  Annotations:

                  • classical conditioning using whisker stimuli expands the representation of trained whiskers (Siucinska &amp; Kossut 1996, 2004),   
            2. perceptual learning
         3. perceptual learning
            1. A1- repeated auditory stimuli

               Annotations:

               • exposing young rats to auditory stimuli enhances the representation of the presented frequencies and intensities in A1, thus altering auditory tuning curves and the tonotopic map (Keuroghlian &amp; Knudsen 2007). 
            2. V1- high contrast oriented gratings

               Annotations:

               •    ·         Presentation of high-contrast oriented gratings to young mice similarly drives orientation-specific enhancement of visual responses in V1 (Frenkel et al. 2006).   
            3. V1- temporally correlated stimuli

               Annotations:

               •    ·         In adult V1, temporally correlated, near-simultaneous stimuli drive systematic shifts in visual tuning related to stimulus order and timing (Dan &amp; Poo 2006).   
            4. S1- temporally correlated stimuli

               Annotations:

               •    ·         Similar potentiation occurs in adult S1 in response to temporal correlations between inputs, leading to neurons and map regions with strong joint representation of temporally correlated inputs (e.g., Diamond et al. 1993, Wang et al. 1995).   
4. Silent synapses
   1. Barrel cortex, young brains

      Annotations:

      •    ·         In the barrel cortex in young brains, silent synapses are abundant (have no AMPA receptors, but have NMDA receptors)   
   2. LTP induction protocols
      1. can insert AMPARs
         1. evidence
            1. failure rates
            2. PPR
5. Methods
   1. experience-dependent map plasticity

      Annotations:

      • the statistical pattern of sensory experience over several days alters topographic sensory maps in primary sensory cortex, in both animals and humans 
      1. barrel cortex- whisker map
      2. sensory deprivation
         1. whiskers
         2. monocular deprivation
   2. sensory perceptual learning

      Annotations:

      • training on sensory perception or discrimination tasks causes gradual improvement in sensory ability associated with changes in neuronal receptive fields and/or maps in cortical sensory areas 
      1. training leads to sensory improvement associated with changes in receptive field/ maps
      2. repeated activation of stimuli- enhances representation of it
      3. temporally associated stimuli- enhances represented link
      4. High contrast stimuli- enhances the differentiated representations
   3. classical conditioning

      Annotations:

      •    &gt;&gt; Training can increase neural responses to reinforced stimuli, shift tuning curves toward (or away from) trained stimuli, or sharpen tuning curves to improve discrimination between stimuli. These changes in neural tuning are generally modest and do not cause large-scale changes in map topography, except with very extensive training.   
      1. small neuronal changes, except with extensive training