Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus

Abstract

The dorsal cochlear nucleus integrates acoustic with multimodal sensory inputs from widespread areas of the brain. Multimodal inputs are brought to spiny dendrites of fusiform and cartwheel cells in the molecular layer by parallel fibers through synapses that are subject to long-term potentiation and long-term depression. Acoustic cues are brought to smooth dendrites of fusiform cells in the deep layer by auditory nerve fibers through synapses that do not show plasticity. Plasticity requires Ca 2؉ -induced Ca 2؉ release; its sensitivity to antagonists of N-methyl-D-aspartate and metabotropic glutamate receptors differs in fusiform and cartwheel cells.A uditory nerve fibers bring acoustic information to the cochlear nucleus and feed it into several parallel pathways that ascend through the brainstem. Pathways through the dorsal cochlear nucleus (DCN) are thought to detect spectral cues for localizing sounds monaurally (1). Those through the ventral cochlear nucleus (VCN) encode spectral and temporal characteristics that allow sounds to be localized in the horizontal plane, through binaural circuits, and recognized.The DCN resembles the cerebellum, cartwheel cells being homologues of cerebellar Purkinje cells (2). Fusiform cells project to the inferior colliculus. Granule cells in the vicinity of the cochlear nuclei are innervated by diverse regions of the brain, including the dorsal column nuclei (1), vestibular periphery (3), and auditory nuclei (4, 5). Their unmyelinated axons, parallel fibers, contact spiny dendrites of fusiform and cartwheel cells. Myelinated auditory nerve fibers contact smooth basal dendrites of fusiform cells. The DCN resembles the electrosensory lobes in fishes even more closely (6, 7).In cerebellar circuits, the gain of one of two converging systems of inputs varies as a function of activity. Long-term depression (LTD) at parallel fiber synapses in cerebellar Purkinje cells evoked by coincident excitation through parallel fiber and climbing fiber synapses plays a role in coordination and motor learning (8). Long-term potentiation (LTP) and LTD at parallel fiber synapses are evoked in electric fishes by convergent excitation by parallel fibers and sensory afferents to compensate for an animal's own signals in localizing external sources (9). We show that principal cells of the DCN combine multimodal inputs through parallel fibers whose strength is modulated by activity with invariant acoustic input through auditory nerve fibers. MethodsCoronal slices (200 m) containing the DCN were prepared from ICR mice (Harlan-Sprague-Dawley) between 18 and 20 days old with an oscillating tissue slicer (VT1000S, Leica Microsystems, Nussloch, Germany). Slices were held in a 300-l chamber that was superfused at 3-5 ml͞min with oxygenated saline at Ϸ33°C. Experiments were done in accordance with the protocols and guidelines of the Animal Care and Use Committee at the University of Wisconsin, Madison.Whole-cell patch-clamp recordings were generally made with 3-to 5-M⍀ pipettes filled with a K-gluconate-base...

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

“…The latter effect might be (at least partly) the consequence of the elimination of the short-term depression present at the parallel fibre-giant cell synapses. Since cholinergic activity simultaneously increases the firing activity of the granule cells, the cholinergic stimulation may contribute to shifting the plasticity of these synapses towards long-term potentiation, similarly to that shown in the cases of the parallel fiber-pyramidal neurone synapses [9].…”

Encoding the Timing of Inhibitory Inputs

“…Because ERK and PKA activity can be regulated by paradigms that generate synaptic plasticity, it is possible that plasticity mechanisms, including those showing sensitivity to spike timing (Bell et al 1997;Feldman 2000;Magee and Johnston 1997;Markram et al 1997;Zhang et al 1998), alter not only synaptic strength, but via actions on specific ion channels also change the relationship between synaptic inputs and spike generation. Such a mechanism could operate in addition to the recently shown synaptic plasticity at the parallel fiber synapses (Fujino and Oertel 2003;Tzounopoulos et al 2004). …”

Assessment of Synaptic Plasticity via Long-Term Potentiation in Young Mice on the Day after Acoustic Trauma: Implications for Tinnitus

“…Many studies identified a significant increase in spontaneous burst frequencies in DCN in cases of tinnitus; others highlighted the multi-layer and organized structure of DCN that facilitated synaptic plasticity induction, such as LTP and long-term depression. LTP can be evoked by an appropriate HFS in fusiform cells because of their cellular and synaptic characteristics [7,15,16] . Synaptic plasticity is classified into long and short term, according to the duration of re-modeling [17] .…”

“…The arithmetic averages of the baseline EPSCs and post-HFS EPSCs between the 5.5 and 10th, 10.5 and 15th, and 15.5 and 20th min were calculated. An increase of ≥10% of post-HFS 5.5th-and 20th-min period according to the baseline EPSCs was referred to LTP generation [7] . LTP recordings were stable during the experiment.…”

“…A total of 30 mice was decapitated on post-natal day 17, and coronal slices were prepared from both DCN [7] . After decapitation, the head was placed in normal physiological saline.…”