Ventral cochlear nucleus responses to contralateral sound are mediated by commissural and olivocochlear pathways

Abstract

In the normal guinea pig, contralateral sound inhibits more than a third of ventral cochlear nucleus (VCN) neurons but excites <4% of these neurons. However, unilateral conductive hearing loss (CHL) and cochlear ablation (CA) result in a major enhancement of contralateral excitation. The response properties of the contralateral excitation produced by CHL and CA are similar, suggesting similar pathways are involved for both types of hearing loss. Here we used the neurotoxin melittin to test the hypothesis that this "compensatory" contralateral excitation is mediated either by direct glutamatergic CN-commissural projections or by cholinergic neurons of the olivocochlear bundle (OCB) that send collaterals to the VCN. Unit responses were recorded from the left VCN of anesthetized, unilaterally deafened guinea pigs (CHL via ossicular disruption, or CA via mechanical destruction). Neural responses were obtained with 16-channel electrodes to enable simultaneous data collection from a large number of single- and multiunits in response to ipsi- and contralateral tone burst and noise stimuli. Lesions of each pathway had differential effects on the contralateral excitation. We conclude that contralateral excitation has a fast and a slow component. The fast excitation is likely mediated by glutamatergic neurons located in medial regions of VCN that send their commissural axons to the other CN via the dorsal/intermediate acoustic striae. The slow component is likely mediated by the OCB collateral projections to the CN. Commissural neurons that leave the CN via the trapezoid body are an additional source of fast, contralateral excitation.

FIG. 1.

Schematic of the pathways to the ventral cochlear nucleus (VCN) of the guinea pig that originate in the contralateral ear. Illustrated are: 1) the direct inhibitory glycinergic pathway via the dorsal/intermediate acoustic striae (D/IAS); 2) direct glutamatergic CN commissural projections via the D/IAS; 3) direct glutamatergic CN commissural projections via the trapezoid body (TB); or 4) cholinergic neurons of the olivocochlear bundle (OCB) that send excitatory collaterals to the VCN. Lesions of the D/IAS (L1) and TB (L2) as they exit the contralateral CN identify whether contralateral excitation is mediated by the D/IAS or the TB. L1 lesions would also disrupt glycinergic inhibition. Lesions of the OCB near the floor of the 4th ventricle (L3) elucidate the role played by the crossed and uncrossed OCB (COCB and UCOCB, respectively) (modified from de Venecia et al. 2005).

FIG. 2.

Example poststimulus time histograms (PSTHs, 100 repeats, 1-ms bin width) of the excitatory responses in a conductive hearing loss (CHL, A) and a cochlear ablation (CA, B) animal. Contralateral sound was broadband noise (BBN, 100-ms duration, 1.5 ms rise-fall time) at 80 db SPL. Responses are from multiunit clusters. The stimulus start time was 25 ms.

FIG. 3.

Rate-level functions for 10 sorted single units in the left VCN of 1 animal. Responses to contralateral (right ear) sound stimulation are shown before and after left cochlear ablation. Stimulus: 100-ms duration BBN. Spike rate is normalized to spontaneous rate. Only 1 unit (Ch 8.1) showed noticeable excitation to contralateral sound before the ablation, but all units were excited post cochlear ablation.

FIG. 4.

Rate-level functions for 10 sorted single units in the left VCN of 1 animal. Responses to ipsilateral (left ear) and contralateral (right ear) sound stimulation are shown after ossicular disruption of the left middle ear. Stimulus: 100-ms duration BBN. Spike rate is normalized to spontaneous rate. As for the cochlear ablation in Fig. 3, most units were excited by contralateral sound following the ossicular disruption.

FIG. 5.

Photomicrograph of a lesion in the D/IAS (L1). An injection of 0.2 μl melittin into the region of the D/IAS, produced a lesion with a rostral-caudal extent of 560 μm that damaged only the D/IAS (arrow). Electrophysiological results from this animal are depicted in Fig. 6, A and B.

FIG. 6.

A: rate-level functions for 3 sorted single units from 1 animal to contralateral sound after cochlear ablation. Responses are shown before and after a melittin lesion in the D/IAS (L1). Spike rate is normalized to spontaneous rate. B: PSTHs of single-unit responses to contralateral sound after cochlear ablation (bin width, 1 ms). Responses shown are pre- and post-lesion (as indicated). Melittin lesion is in the D/IAS (L1). Photomicrographs of the lesion in this animal are shown in Fig. 5. Stimulus: 100-ms duration BBN.

FIG. 7.

Rate-level functions for 11 multiunit recording sites from 1 animal to contralateral sound after cochlear ablation; from a different animal than the 1 shown in Fig. 6, A and B. Responses are shown before (A) and after (B) a melittin lesion in the D/IAS (L1). Stimulus: 100-ms duration BBN.

FIG. 8.

Photomicrograph of a lesion in the trapezoid body (TB; L2). Following an injection of 0.3 μl melittin into the ventral region of the superior olivary complex (SOC), a small lateral lesion of the TB is observed with a rostral-caudal extent of 350 μm. The lesion began in the most caudal regions of the SOC, and damaged only the trapezoid body (TB, arrow). Electrophysiological results from this animal are depicted in Fig. 9, A and B.

FIG. 9.

A: rate-level functions for 3 sorted single units from 1 animal to contralateral sound after cochlear ablation. Responses are shown before and after a melittin lesion in the TB (L2.) Spike rate is normalized to spontaneous rate. B: PSTHs of single-unit responses to contralateral sound after cochlear ablation (bin width, 1 ms). Responses shown are pre- and postlesion (as indicated). Melittin lesion is in the TB (L2). Photomicrograph of the lesion in this animal is shown in Fig. 8. Stimulus: 100-ms duration BBN.

FIG. 10.

Rate-level functions for 13 multiunit recording sites from 1 animal to contralateral sound after cochlear ablation. From a different animal than the 1 shown in Fig. 9, A and B. Responses are shown before (A) and after (B) a melittin lesion in the trapezoid body (L2). Stimulus: 100-ms duration BBN.

FIG. 11.

Photomicrograph of a lesion of the olivocochlear bundle (OCB; L3). An injection of 0.3 μl melittin produced a lesion with a rostral-caudal extent of 720 μm that appeared to damage only the OCB (see arrow). The cochlear nucleus on the left is folded over the section. Electrophysiological results from this animal are depicted in Fig. 12, A and B.

FIG. 12.

A: rate-level functions for 3 sorted single units from 1 animal to contralateral sound after cochlear ablation. Responses are shown before and after a melittin lesion of the OCB (L3). Spike rate is normalized to spontaneous rate. B: PSTHs of single-unit responses to contralateral sound after cochlear ablation (bin width, 1 ms). Responses shown are pre- and postlesion (as indicated). Melittin lesion is in the OCB (L3). Photomicrograph of the lesion in this animal is shown in Fig. 11. Stimulus: 100-ms duration BBN.

FIG. 13.

Rate-level functions for 14 multiunit recording sites from 1 animal to contralateral sound after cochlear ablation. From a different animal than the 1 shown in Fig. 12, A and B. Responses are shown before (A) and after (B) a melittin lesion in the OCB (L3). Stimulus: 100-ms duration BBN.