Biomedical subjects

Patrick O Kanold

Publications and source records attributed to Patrick O Kanold.

6 recordsLinked to original sources

PubMed2006

Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity.

Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.

Animals↗

PubMed2006

PirB restricts ocular-dominance plasticity in visual cortex.

Experience can alter synaptic connectivity throughout life, but the degree of plasticity present at each age is regulated by mechanisms that remain largely unknown. Here, we demonstrate that Paired-immunoglobulin-like receptor B (PirB), a major histocompatibility complex class I (MHCI) receptor, is expressed in subsets of neurons throughout the brain. Neuronal PirB protein is associated with synapses and forms complexes with the phosphatases Shp-1 and Shp-2. Soluble PirB fusion protein binds to cortical neurons in an MHCI-dependent manner. In mutant mice lacking functional PirB, cortical ocular-dominance plasticity is more robust at all ages. Thus, an MHCI receptor is expressed in central nervous system neurons and functions to limit the extent of experience-dependent plasticity in the visual cortex throughout life. PirB is also expressed in many other regions of the central nervous system, suggesting that it may function broadly to stabilize neural circuits.

Aging↗

PubMed2005

Multiple periods of functional ocular dominance plasticity in mouse visual cortex.

The precise period when experience shapes neural circuits in the mouse visual system is unknown. We used Arc induction to monitor the functional pattern of ipsilateral eye representation in cortex during normal development and after visual deprivation. After monocular deprivation during the critical period, Arc induction reflects ocular dominance (OD) shifts within the binocular zone. Arc induction also reports faithfully expected OD shifts in cat. Shifts towards the open eye and weakening of the deprived eye were seen in layer 4 after the critical period ends and also before it begins. These shifts include an unexpected spatial expansion of Arc induction into the monocular zone. However, this plasticity is not present in adult layer 6. Thus, functionally assessed OD can be altered in cortex by ocular imbalances substantially earlier and far later than expected.

Age Factors↗

PubMed2004

Encoding the timing of inhibitory inputs.

Many neuronal systems represent information by the timing of individual spikes, and it is generally assumed that spike timing predominantly encodes excitatory inputs. We show here that the timing of inhibition can also be explicitly encoded in spike times using time-dependent and voltage-dependent properties of a rapidly inactivating potassium channel (I(KIF)). In vitro recordings in rat dorsal cochlear nucleus show that the effects of inhibition on spike timing can long outlast the duration of the inhibitory potential and that this depends only on the membrane voltage change during the inhibitory postsynaptic potential. Modeling results show that small neuronal populations with a heterogeneous distribution of I(KIF) voltage dependence can robustly encode intervals of >100 ms between inhibition and excitation. Thus neuronal systems can detect and represent the precise timing of inhibition, suggesting the importance of inhibition in information encoding.

Action Potentials↗

PubMed2004

Transient microcircuits formed by subplate neurons and their role in functional development of thalamocortical connections.

Subplate neurons are a transient population of neurons in the brain forming one of the first functional cortical circuits. Past experiments have demonstrated their importance in growth of thalamocortical afferents into the cortical plate and later segregation of thalamocortical afferents. Recently, subplate neurons have been shown to be required for the functional maturation of both thalamocortical connections and mature visual responses in visual cortex. These findings suggest that thalamocortical afferents might not segregate properly in the absence of subplate neurons because the thalamocortical synapse does not mature. Subplate neurons are unique in that they form a circuit that appears to promote synaptic scaling and maturation. Although the precise contribution of subplate neurons within the context of cortical development is unknown, they might play an early role in providing thalamic input to cortex that then interacts with learning rules governing synaptic strengthening at the thalamocortical synapse. Because they appear to play multiple key roles at different stages of development, subplate neurons might also play a role in the pathology of developmental disorders, such as epilepsy and schizophrenia.

Animals↗

PubMed2003

Role of subplate neurons in functional maturation of visual cortical columns.

The subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that subplate ablation also prevents formation of orientation columns. Visual responses are weak and poorly tuned to orientation. Furthermore, thalamocortical synaptic transmission fails to strengthen, whereas intracortical synapses are unaffected. Thus, subplate circuits are essential not only for the anatomical segregation of thalamic inputs but also for key steps in synaptic remodeling and maturation needed to establish the functional architecture of visual cortex.

Animals↗