| Summary: | Neurons in the ventral medial geniculate body (MGBv) of the thalamus transform
auditory signals and participate in corticothalamic oscillations, depending on the behavioral state.
To study the role of intrinsic membrane properties and neuromodulation on the signal
transformation of MGBv neurons, whole-cell patch-clamp recordings and pharmacological
analyses were performed in rat brain slice preparations. The neurons were labelled and
morphologically characterized by immunohistochemical methods.
In all mature MGBv neurons, current injections produced a range of voltage-dependent
firing patterns. At depolarized membrane potentials, observed previously during wakefulness in
vivo, the neurons fired tonically with different latencies. In contrast, at hyperpolarized potentials
low-threshold burst firing was observed, which has been implicated in the generation of deltaoscillations
during deep sleep. Na⁺-, Ca²⁺-, K⁺- and mixed cationic conductances were found to
contribute to subthreshold rectification and the action potential patterns. High-threshold Ca²⁺-
spikes were identified for the first time in MGBv as part of the burst response and may play a
role in dendritic signalling. Thus the intrinsic membrane properties influence timing and quality
of spikes during the different tonic and burst firing modes, with important implications for
auditory signalling and sleep oscillations.
The intrinsic membrane properties endow MGBv neurons with frequency filter
properties. Using frequency analysis methods (ZAP analysis), a membrane resonance at 1-2 Hz
was found at hyperpolarized potentials, due to an interaction of the low-threshold T-type Ca²⁺-
conductance with the passive membrane properties. At more depolarized potentials, the
membrane exhibited low-pass filter characteristics. These frequency preferences were modulated
by activation of subthreshold Na⁺- and K⁺- conductances. Firing of Na⁺- and high-threshold
Ca²⁺-spikes occurred most readily at the preferred frequencies. Thus the resonance at 1-2 Hz
confers properties of a band-pass frequency filter on MGBv neurons, which may contribute to the
generation and synchronization of delta oscillations during slow-wave sleep.
Postnatal development in MGBv neurons changes dendritic morphology, intrinsic
membrane properties, firing patterns and frequency preferences: the dendritic trees increased in
size and complexity; the resting membrane potentials and input resistance decreased, while
action potential and low-threshold Ca²⁺-spike amplitude and rate of rise increased over the first
two postnatal weeks. Immature neurons exhibited high-threshold Ca -spikes appended to action
potentials during tonic firing, but no low-threshold burst firing could be evoked.
The development was concluded by day 12-15, when full auditory function and the characteristic
behavioral states of mature animals are observed.
Activation of metabotropic glutamate and GABA[sub B] receptors change signal transformation
in MGBv neurons. Application of the selective metabotropic glutamate receptor agonist 1S,3RACPD
reversibly depolarized MGBv neurons, changing burst to tonic firing and the 1-2 Hz
resonance to low-pass filter properties. This depolarization was produced by activation of a
TTX- insensitive Na⁺-dependent current without a change in input conductance between -40 and
-85 mV, a novel finding in thalamic neurons. Actions on K⁺-currents were ruled out, as the K⁺-
channel blockers Ba2 +and Cs+ and changes in extracellular K⁺ had no effects on the evoked
1S.3R-ACPD- current. The effects of IS, 3R-ACPD were blocked by the metabotropic
glutamate receptor antagonist MCPG. Irreversible activation or blockade of the 1S.3R-ACPDcurrent
by intracellular application of the GTP analogs GTP7S and GDPPS, respectively,
suggested an involvement of G-proteins in intracellular signal transduction. These metabotropic
glutamate effects may play a role in corticothalamic modulation of auditory signal transmission.
Activation of GABA[sub B] receptors by the selective agonist baclofen reversibly
hyperpolarized MGBv neurons by activation of a Ba²⁺-sensitive K⁺-current, which increased the
input conductance. The conductance increase shunted the 1-2 Hz resonance. The effect of
baclofen was blocked by application of the GABA[sub B] receptor antagonist CGP 35348. The
occlusion and blockade of baclofen effects by the GTP analogs GTP7S and GDPpS, respectively,
confirmed an involvement of G-protein activation. The GABA[sub B] receptors may mediate longerlasting
inhibitory potentials from the inferior colliculus and the thalamic reticular nucleus, which
have been implicated in the modulation of sleep and pathological oscillations.
Application of the volatile anesthetic isoflurane reversibly hyperpolarized MGBv neurons
and shunted firing in both tonic and burst modes. Moreover, isoflurane eliminated the resonance
at 1-2 Hz. These effects may play a role in the disruption of auditory signal transduction and
oscillations by general anesthetics.
These investigations have identified for the first time intrinsic membrane properties and
neuromodulatory effects in MGBv neurons, which may explain the fundamental differences in
auditory information processing during diverse behavioral states (wakefulness, sleep and
anesthesia).
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