Study identifies cause of dendritic pruning defect linked to autism and schizophrenia.

Memories are formed at structures in the brain known as dendritic spines which communicate with other brain cells via synapses. It is known that the number of these brain connections decreases by half after puberty, a finding shown in brain areas for many species, including humans and rodents.  This process, known as adolescent ‘synaptic pruning’, is thought to be important for normal learning in adulthood.

Synaptic pruning is believed to remove unnecessary synaptic connections to make room for relevant new memories, however, because this process is disrupted in diseases such as autism and schizophrenia, there has recently been widespread interest in the subject.  Now, a study from researchers led by SUNY Downstate Medical Center identifies a brain receptor which appears to initiate adolescent synaptic pruning, and that appears to go awry in both autism and schizophrenia.  The team state that their study is the first to identify the process which initiates synaptic pruning at puberty.  The opensource study is published in the journal elife.

Previous studies have shown that during puberty the density of dendritic spines decreases by half in widespread areas of the CNS.  This includes the CA1 hippocampus and temporal lobe of both rodents and humans which are sites essential for learning and memory. However, despite the implied importance of synaptic pruning during adolescence, the mechanisms underlying spine elimination in the CA1 hippocampus during puberty are not yet known, nor are the resulting developmental disorders due to altered spine density.  One factor yet to be considered in adolescent pruning is the role of inhibition in the brain mediated by GABA receptors (GABARs).  Earlier studies from the lab show that at puberty, there is an increase in inhibitory GABARs, which are targets for brain chemicals that quiet down nerve cells.  The current study shows that adolescent pruning requires GABARs and, in their absence, pruning is prevented which affects cognition.

The current study utilises a GABAR knock-out mouse-model to show that pruning does not take place, and the cognitive ability of post-pubertal mice is impaired. Results show that GABA receptors trigger synaptic pruning at puberty in the mouse hippocampus, a brain area involved in learning and memory.  Data findings show that by reducing brain activity, these GABA receptors also reduce levels of a protein in the dendritic spine, known as kalirin-7, which stabilizes the scaffolding in the spine to maintain its structure.

Results show that mice which do not have these GABA receptors do not undergo synaptic pruning, and maintain the same high-level of brain connections throughout adolescence.  Data findings show that the mice with too many brain connections are able to learn spatial locations, but are unable to re-learn new locations after this initial learning, suggesting that too many brain connections may limit learning potential.

The team surmise that their findings are highly salient as it has been shown children with autism have an over-abundance of synapses in some parts of the brain. They go on to add other research suggests that prefrontal brain areas in people with schizophrenia have fewer neural connections than the brains of those who do not have the condition. For the future, the researchers state that their data may suggest new treatments targeting GABA receptors for normalizing synaptic pruning in diseases such as autism and schizophrenia, where synaptic pruning is abnormal.

Source: SUNY Downstate Medical Center

Origin of synaptic pruning process linked to learning, autism and schizophrenia identified - neuroinnovations

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