Results: 3

1.
Figure 2

Figure 2. Loss or gain of protein or RNA function results in altered neuronal homeostasis or ‘imbalance’. From: Failure of neuronal homeostasis results in common neuropsychiatric phenotypes.

Homeostasis is represented by the balance of a weighted ball floating in water. Individual proteins involved in the following syndromes are each represented by a coloured shape. a, Representation of a healthy neuron, with proteins in balance. b, Representation of a neuron in fragile X syndrome, with normal dendrites but an increased density of longer, thinner, immature-appearing dendritic spines. c, Representation of a neuron in Angelman syndrome, with normal dendrites but a decreased density of, and abnormally shaped, dendritic spines. d, Representation of a neuron in Rett syndrome or Mecp2-null mice, with decreased density of dendrites and decreased density of, and abnormally shaped, synapses (represented by dendritic spines). e, Representation of a neuron from mice in which Mecp2 is duplicated, with increased density of synapses (represented by increased density of dendrites and dendritic spines).

Melissa B. Ramocki, et al. Nature. ;455(7215):912-918.
2.
Figure 1

Figure 1. Loss of protein or RNA function causes neurodevelopmental disorders with phenotypes overlapping those caused by gain of protein or RNA function. From: Failure of neuronal homeostasis results in common neuropsychiatric phenotypes.

Each pair of ovals demonstrates loss and duplication of the same chromosomal region. Phenotypes unique to loss of function are shown in yellow; phenotypes unique to gain of function are shown in blue; phenotypes common to both loss of function and gain of function are shown in green. Each of these alterations in neuronal function converges on pathways that cause mental retardation and autism or abnormal behaviours. (Both Prader–Willi syndrome (PWS) and Angelman syndrome (bottom) involve deletion of 15q11–q13.) MECP2, gene encoding methyl-CpG-binding protein 2; PLS, Potocki–Lupski syndrome; SMS, Smith–Magenis syndrome; WBS, Williams–Beuren syndrome.

Melissa B. Ramocki, et al. Nature. ;455(7215):912-918.
3.
Figure 3

Figure 3. Homeostatic responses could result in a compensated neuronal network with decreased flexibility. From: Failure of neuronal homeostasis results in common neuropsychiatric phenotypes.

The curves show how synaptic output varies with the concentration of a given protein (X). Synaptic output is the product of synapse number and the synaptic strength per individual synapse. Protein X represents any protein important to synaptic strength and learning, for example, the AMPA receptor. The horizontal dashed line represents the ideal level of synaptic output (red circles). The middle curve (wild type) represents the normal situation. Point A is the concentration of X necessary to produce an ideal synaptic output. The neuron is flexible; in response to any learning event or stimulus, it can rapidly increase or decrease synaptic output (blue circles) with minimal change in the concentration of protein X (because the neuron exists in an ideal state represented by point A being on the steep portion of the curve). In cases in which there is a permanent loss or gain of the activity of a specific molecule (thin and thick curves, respectively), homeostatic changes in protein X occur to restore appropriate synaptic output (points B and C, respectively). At these new steady states, however, the neuron no longer retains the flexibility necessary to adequately respond to a learning or extinction stimulus (because points B and C are on flatter regions of the curve). Therefore, the dynamic ability of the neuronal system to respond is weakened, and phenotypes such as mental retardation and autism can result.

Melissa B. Ramocki, et al. Nature. ;455(7215):912-918.

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