The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus

Abstract

Acoustic information is brought to the brain by auditory nerve fibers, all of which terminate in the cochlear nuclei, and is passed up the auditory pathway through the principal cells of the cochlear nuclei. A population of neurons variously known as T stellate, type I multipolar, planar multipolar, or chopper cells forms one of the major ascending auditory pathways through the brainstem. T Stellate cells are sharply tuned; as a population they encode the spectrum of sounds. In these neurons, phasic excitation from the auditory nerve is made more tonic by feedforward excitation, coactivation of inhibitory with excitatory inputs, relatively large excitatory currents through NMDA receptors, and relatively little synaptic depression. The mechanisms that make firing tonic also obscure the fine structure of sounds that is represented in the excitatory inputs from the auditory nerve and account for the characteristic chopping response patterns with which T stellate cells respond to tones. In contrast with other principal cells of the ventral cochlear nucleus (VCN), T stellate cells lack a low-voltage-activated potassium conductance and are therefore sensitive to small, steady, neuromodulating currents. The presence of cholinergic, serotonergic and noradrenergic receptors allows the excitability of these cells to be modulated by medial olivocochlear efferent neurons and by neuronal circuits associated with arousal. T Stellate cells deliver acoustic information to the ipsilateral dorsal cochlear nucleus (DCN), ventral nucleus of the trapezoid body (VNTB), periolivary regions around the lateral superior olivary nucleus (LSO), and to the contralateral ventral lemniscal nuclei (VNLL) and inferior colliculus (IC). It is likely that T stellate cells participate in feedback loops through both medial and lateral olivocochlear efferent neurons and they may be a source of ipsilateral excitation of the LSO.

Figure 1

Reconstruction of a T stellate cell in a slice of the cochlear nuclear complex. The cell was labeled with biocytin in a slice of living tissue. The cell was reconstructed with a camera lucida from sections of the slice that had been processed to visualize cells with methods that have been described (Golding et al., 1995). The soma of this cell lies at the indistinct border between the anteroventral (aVCN) and posteroventral (pVCN) cochlear nuclei, just dorsal to the nerve root (nr). As is characteristic of T stellate cells, its dendrites lie parallel to the path of the ascending and descending branches of auditory nerve fibers with the highly branched tips in the vicinity of overlying granule cells. The axon emanates from the cell body. One branch projects dorsally through the granule cell lamina (gr) into the deep layer (dl) of the dorsal cochlear nucleus (DCN). The terminal arbor occupies an isofrequency lamina that crosses the deep layer but does not extend into the fusiform cell layer (fcl) or the molecular layer (ml). The main axon was cut at the medial surface of the slice where it projected into the trapezoid body (*).

Figure 2

T Stellate cells fire tonically in response to tones. A. An intracellular recording from a T stellate cell in a cat shows that the cell fired steadily for the duration of the 50-msec tone at the cell’s characteristic frequency and that the firing became more rapid with increasing intensity. B. Peristimulus time histogram from the same cell as in A generated from responses to 250 repetitions of tones at the characteristic frequency. C. Chopper fires at an almost constant rate for the duration of a 500 msec tone at the characteristic frequency. Bin width for computing histogram was 3.9 ms. D. In contrast with choppers, primary-like neurons fire rapidly at the onset of a tone and then more slowly as they adapt. Figures A and B are by Rhode and Smith, reproduced from the Journal of Neurophysiology, 1986, Am Physiol Soc, used with permission, and C and D are by Blackburn and Sachs, reproduced from the Journal of Neurophysiology, 1989, Am Physiol Soc, used with permission.

Figure 3

T Stellate cells integrate neuromodulatory with driving inputs. A. Indirect evidence indicates that inputs to T stellate cells are to some extent spatially segregated. Intracellular recordings with electrodes at the soma reveal glutamatergic (Glu) and glycinergic (Gly) synaptic responses. The rapid rise of those synaptic responses is consistent with their being generated near the soma. There are several known sources for these excitatory and inhibitory inputs. Even GABAergic synaptic responses mediated through GABA_A receptors are so slow and small that individual PSPs are difficult to resolve suggesting that they are generated distally in dendrites, which is also consistent with the location of GABAergic terminals from Golgi and Periolivary cells in granule cell regions. T Stellate cells have nicotinic and muscarinic acetylcholine receptors. Cholinergic fibers terminate near the tips of T stellate cell dendrites near the granule cell domains . Noradrenergic and serotonergic fibers course throughout the VCN suggesting that they can contact dendrites of T stellate cells either or both proximally or distally. B. A T stellate cell was excited by the bath-application of neuromodulators. A whole-cell patch-clamp recording made with a pipette that contained a gluconate-based, GTP-containing solution in the presence of 1 µM strychnine and 40 µM 6,7-dinitroquinoxaline-2,3-dione (DNQX) in the extracellular saline solution to block glutamatergic and glycinergic synaptic responses, shows that both serotonin and norepinephrine reversibly evoked spontaneous firing. The application of serotonin did not change the resting potential, shown by the numbers at the left of the traces in mV, and responses to hyperpolarizing current pulses (− 0.4 and − 0.5 nA) indicate that the change in input resistance was too small to be detected. Serotonin increased firing after the end of the hyperpolarizing pulse. After the serotonin was washed out, norepinephrine increased spontaneous and anode break firing in the same cell. All effects were reversible. Details of the methods have been described previously (Fujino and Oertel, 2001).

Figure 4

T Stellate cells project widely. Local collaterals innervate the ventral (VCN) and dorsal (DCN) cochlear nuclei. The main axon projects out through the trapezoid body, innervates the region around the ipsilateral lateral superior olivary nucleus (LSO), crosses the midline, innervates the contralateral ventral nucleus of the trapezoid body (VNTB), ventral nucleus of the lateral lemniscus (VNLL) and ultimately terminates in the contralateral inferior colliculus. Occasionally T stellate cells innervate the ipsilateral intermediate nucleus of the lateral lemniscus (INLL), dorsal nucleus of the lateral lemniscus (DNLL) and the ipsilateral inferior colliculus.