Sparse but Selective and Potent Synaptic Transmission From the Globus Pallidus to the Subthalamic Nucleus
Journal of Neurophysiology. 2009-07-01; 102(1): 532-545
Lire sur PubMed
1. J Neurophysiol. 2009 Jul;102(1):532-45. doi: 10.1152/jn.00305.2009. Epub 2009 May
Sparse but selective and potent synaptic transmission from the globus pallidus to
the subthalamic nucleus.
Baufreton J(1), Kirkham E, Atherton JF, Menard A, Magill PJ, Bolam JP, Bevan MD.
(1)Department of Physiology, Northwestern University, 303 E. Chicago Ave,
Chicago, Il 60611, USA.
The reciprocally connected GABAergic globus pallidus (GP)-glutamatergic
subthalamic nucleus (STN) network is critical for voluntary movement and an
important site of dysfunction in movement disorders such as Parkinson’s disease.
Although the GP is a key determinant of STN activity, correlated GP-STN activity
is rare under normal conditions. Here we define fundamental features of the
GP-STN connection that contribute to poorly correlated GP-STN activity.
Juxtacellular labeling of single GP neurons in vivo and stereological estimation
of the total number of GABAergic GP-STN synapses suggest that the GP-STN
connection is surprisingly sparse: single GP neurons maximally contact only 2% of
STN neurons and single STN neurons maximally receive input from 2% of GP neurons.
However, GP-STN connectivity may be considerably more selective than even these
estimates imply. Light and electron microscopic analyses revealed that single GP
axons give rise to sparsely distributed terminal clusters, many of which
correspond to multiple synapses with individual STN neurons. Application of the
minimal stimulation technique in brain slices confirmed that STN neurons receive
multisynaptic unitary inputs and that these inputs largely arise from different
sets of GABAergic axons. Finally, the dynamic-clamp technique was applied to
quantify the impact of GP-STN inputs on STN activity. Small fractions of GP-STN
input were sufficiently powerful to inhibit and synchronize the autonomous
activity of STN neurons. Together these data are consistent with the conclusion
that the rarity of correlated GP-STN activity in vivo is due to the sparsity and
selectivity, rather than the potency, of GP-STN synaptic connections.
PMID: 19458148 [Indexed for MEDLINE]