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Alterations of neocortical pyramidal neurons: turning points in the genesis of mental retardation.

Granato A, De Giorgio A - Front Pediatr (2014)

Bottom Line: Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs.Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol.Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Catholic University , Milan , Italy.

ABSTRACT
Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration showing different types of PNs. In layer 2/3, neurons are interconnected to form distinct subnetworks (green and red cells). In the barrel cortex, lemniscal (Lem) and paralemniscal (PLem) afferents target different subpopulations (purple and orange cells). In layer 5, regular spiking PNs (RS, black) and intrinsically bursting PNs (IB, blue) display different dendritic morphologies and different projections.
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Figure 1: Schematic illustration showing different types of PNs. In layer 2/3, neurons are interconnected to form distinct subnetworks (green and red cells). In the barrel cortex, lemniscal (Lem) and paralemniscal (PLem) afferents target different subpopulations (purple and orange cells). In layer 5, regular spiking PNs (RS, black) and intrinsically bursting PNs (IB, blue) display different dendritic morphologies and different projections.

Mentions: Santiago Ramón y Cajal referred to the neocortical pyramidal neuron (PN) as “La noble y enigmática célula del pensamiento” (the noble and enigmatic cell of thought) (1). These glutamatergic, excitatory neurons represent the vast majority of neocortical cells (about 80–90%), the remaining being constituted by GABAergic, inhibitory interneurons. Surprisingly and contrary to what one may expect, cortical interneurons, though minor in number, are characterized by a great variety of anatomical features, electrophysiological properties, and synaptic attributes [see Ref. (2) for review]. Conversely, PNs are often conceived as a rather homogeneous population. However, the principal neurons of the cerebral cortex are far from being identical to each other, since they show both evident and more subtle differences (Figure 1). In the present mini-review, we will first provide some examples of how PNs represent a heterogeneous population. Then, while it is quite obvious that developmental disorders associated with mental retardation (MR) target the main structure involved in cognitive functions (i.e., the cerebral cortex) and its majority neurons, we try to answer the question whether given subpopulations or functional features of PNs are preferentially affected. We focus mainly on the effects of fetal exposure to alcohol (see Figure 2), highlighting analogies and differences with other developmental disorders associated with MR.


Alterations of neocortical pyramidal neurons: turning points in the genesis of mental retardation.

Granato A, De Giorgio A - Front Pediatr (2014)

Schematic illustration showing different types of PNs. In layer 2/3, neurons are interconnected to form distinct subnetworks (green and red cells). In the barrel cortex, lemniscal (Lem) and paralemniscal (PLem) afferents target different subpopulations (purple and orange cells). In layer 5, regular spiking PNs (RS, black) and intrinsically bursting PNs (IB, blue) display different dendritic morphologies and different projections.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127660&req=5

Figure 1: Schematic illustration showing different types of PNs. In layer 2/3, neurons are interconnected to form distinct subnetworks (green and red cells). In the barrel cortex, lemniscal (Lem) and paralemniscal (PLem) afferents target different subpopulations (purple and orange cells). In layer 5, regular spiking PNs (RS, black) and intrinsically bursting PNs (IB, blue) display different dendritic morphologies and different projections.
Mentions: Santiago Ramón y Cajal referred to the neocortical pyramidal neuron (PN) as “La noble y enigmática célula del pensamiento” (the noble and enigmatic cell of thought) (1). These glutamatergic, excitatory neurons represent the vast majority of neocortical cells (about 80–90%), the remaining being constituted by GABAergic, inhibitory interneurons. Surprisingly and contrary to what one may expect, cortical interneurons, though minor in number, are characterized by a great variety of anatomical features, electrophysiological properties, and synaptic attributes [see Ref. (2) for review]. Conversely, PNs are often conceived as a rather homogeneous population. However, the principal neurons of the cerebral cortex are far from being identical to each other, since they show both evident and more subtle differences (Figure 1). In the present mini-review, we will first provide some examples of how PNs represent a heterogeneous population. Then, while it is quite obvious that developmental disorders associated with mental retardation (MR) target the main structure involved in cognitive functions (i.e., the cerebral cortex) and its majority neurons, we try to answer the question whether given subpopulations or functional features of PNs are preferentially affected. We focus mainly on the effects of fetal exposure to alcohol (see Figure 2), highlighting analogies and differences with other developmental disorders associated with MR.

Bottom Line: Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs.Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol.Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Catholic University , Milan , Italy.

ABSTRACT
Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus