Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body.

摘要

Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the second GABA(A) potential amplitude measured from the resting potential, but the GABA(B) amplitude was sensitive to the interstimulus interval. Train stimuli applied to collicular or cortical inputs generated intra-train responses that were often predicted by their paired-pulse behavior. Long-lasting responses following train stimulation of the collicular inputs were uncommon. In contrast, corticothalamic inputs often generated long-lasting depolarizing responses that were dependent on activation of a metabotropic glutamate receptor.Our results demonstrate that during repetitive afferent firing there are input-specific mechanisms controlling synaptic strength and membrane potential over short and long time scales. Furthermore, they suggest that there may be two classes of excitatory collicular input to medial geniculate neurons and a single class of small-terminal corticothalamic inputs, each of which has distinct features.