Low-frequency thalamocortical oscillations that underlie drowsiness and slow-wave sleep depend on rhythmic inhibition of relay cells by neurons in the reticular nucleus (RTN) under the influence of corticothalamic fibers that branch to innervate RTN neurons and relay neurons. To generate oscillations, input to RTN predictably should be stronger so disynaptic inhibition of relay cells overcomes direct corticothalamic excitation. Amplitudes of excitatory postsynaptic conductances (EPSCs) evoked in RTN neurons by minimal stimulation of corticothalamic fibers were 2.4 times larger than in relay neurons, and quantal size of RTN EPSCs was 2.6 times greater. GluR4-receptor subunits labeled at corticothalamic synapses on RTN neurons outnumbered those on relay cells by 3.7 times, providing a basis for differences in synaptic strength. reticular nucleus ͉ ventral posterior nucleus ͉ dual whole-cell recordings ͉ minimal stimulation ͉ synaptic strength C orticothalamic fibers that arise from layer VI cells in the cerebral cortex branch to innervate neurons in the reticular nucleus (RTN) and thalamocortical relay neurons in the underlying thalamus (1, 2) are a powerful influence in the generation of neuronal synchrony in thalamus and cortex (3). In RTN and relay nuclei, they end in excitatory synapses associated with ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate, and metabotropic glutamate receptors (4-8). Corticothalamic fibers strongly excite inhibitory neurons of the RTN and these in turn inhibit relay neurons. Relay neurons fire bursts of action potentials as they recover from inhibition, re-exciting RTN cells so that the sequence continues (9-11). The capacity of the disynaptic RTN-generated inhibitory postsynaptic potential (IPSP) to overcome the monosynaptic excitatory postsynaptic potential (EPSP) generated by the direct corticothalamic input to the relay neurons is a key element in generation of low-frequency oscillations or spindle waves (10, 12), which are the electroencephalographic hallmarks of drowsiness and early stages of slow-wave sleep. In models in which the strength of corticothalamic input to RTN neurons is set equal to that to relay neurons, the disynaptic IPSP is shunted by the monosynaptic EPSP, and the network does not oscillate (13). Here, we demonstrate that excitatory postsynaptic conductances (EPSCs) elicited by minimal stimulation of corticothalamic fibers are stronger quantitatively in RTN than in ventral posterior thalamic nucleus (VP) neurons, and that the number of GluR4 subunits at corticothalamic synapses on RTN neurons is correspondingly greater than at synapses on relay cells, providing a basis for synaptic heterogeneity.
Materials and MethodsWhole-cell recordings were made at 22-25°C from neurons in layer VI of somatosensory cortex, RTN, and VP in brain slices from postnatal day 13 to 24 ICR mice, cut at an angle that preserves corticothalamic and thalamocortical connectivity, and maintained in vitro as described (14). Electrode resistances were 2-5 M...