Physiological characteristics of postinhibitory rebound depolarization in neurons of the rat's dorsal cortex of the inferior colliculus studied in vitro

doi:10.1016/j.brainres.2008.06.010

Brain Research

Volume 1226, 21 August 2008, Pages 70-81

https://doi.org/10.1016/j.brainres.2008.06.010 Get rights and content

Abstract

The inferior colliculus (IC) is a major center for neural integration in the auditory pathway. The IC processes inputs from the lower brainstem as well as from higher centers in the auditory system. To understand cellular mechanisms of IC neurons in auditory processing, we investigated physiological characteristics of the rebound depolarization (RD) following membrane hyperpolarization in neurons of the rat's dorsal cortex of the inferior colliculus (ICD). Whole-cell patch clamp recordings were made from ICD neurons in brain slices. In more than half of the ICD neurons, there was a RD accompanied by one or two anode break action potentials (APs) following membrane hyperpolarization. The RD was Ca²⁺ mediated and primarily due to activation of low-threshold T-type Ca²⁺ channels. Generation of the RD and anode break APs depended on the magnitude and duration of the preceding hyperpolarization. Larger and longer hyperpolarization induced a larger, shorter and faster rebound, and therefore earlier anode break APs. However, with further hyperpolarization the RD became constant in amplitude and duration despite increases in the strength or duration of the preceding hyperpolarization. Usually, membrane hyperpolarization as small as − 15 mV for 100–200 ms was enough to induce a pronounced rebound of 15–20 mV. The RD in IC neurons may provide a neuronal mechanism for integrating excitatory inputs arriving soon after a period of synaptic inhibition and therefore processing specific aspects of auditory information.

Introduction

The inferior colliculus (IC) is a major center for neural integration in the auditory midbrain. The IC plays an important role in processing not only basic attributes of sounds, i.e., spectrum, intensity, temporal structure, but also specific characteristics of sounds that are relevant to an animal's communication and behavior (Chiu and Poon, 2000, Covey and Casseday, 1999, Ehret and Schneiner, 2005, Ehrlich et al., 1997, Fuzessery et al., 2006, Zhang and Kelly, 2003). The IC can be divided into three anatomical subdivisions, the central nucleus (ICC), external (or lateral) cortex (ICX) and dorsal cortex (ICD) (Faye-Lund and Osen, 1985, Loftus et al., 2008). The ICC and ICD receive inputs from the auditory nuclei in the lower (Malmierca et al., 2005, Oliver, 1984, Oliver, 1987, Oliver et al., 1995) and higher (Winer et al., 1998) levels of the auditory pathway, and project to neurons within the auditory system (see reviews, Cant, 2005, Malmierca and Merchán, 2004, Oliver, 2005, Schofield, 2005, Winer and Schreiner, 2005). On the other hand, the ICX is considered to be a multisensory nucleus with substantial connections to both somatosensory and auditory structures (Malmierca, 2003, Malmierca and Merchán, 2004, Shore and Zhou, 2006, Zhou and Shore, 2006).

Intracellular studies have shown several distinct types of intrinsic membrane properties in ICC (Li et al., 1998, Peruzzi et al., 2000, Sivaramakrishna and Oliver, 2001), ICD (Li et al., 1998, Smith, 1992, Sun and Wu, 2008) and ICX (Ahuja and Wu, 2007, Li et al., 1998, Smith, 1992) neurons. Some of the intrinsic membrane properties of neurons among the three subdivisions of the IC are very similar. In response to depolarizing current injection, the majority of IC neurons show a sustained firing pattern, including regular and adapting firing. Some other neurons display a buildup or a pause-buildup pattern. A small proportion of IC neurons show an onset or a transient firing pattern. In response to hyperpolarizing current injection, a striking feature is rebound depolarization (RD). Approximately half of the ICC and ICD neurons, and some ICX neurons exhibit a RD, often accompanied by one or two anode break action potentials (APs), following membrane hyperpolarization (Ahuja and Wu, 2007, Sivaramakrishna and Oliver, 2001, Sun and Wu, 2008).

RD has been observed in many neurons in other regions of the brain, including cerebellum, hippocampus, thalamus, subthalmus and hypothalamus (Aizenman and Linden, 1999, Bevan et al., 2002, Fan et al., 2000, Surges et al., 2006; Szkudlarek and Raastad, 2007). Most of the neurons exhibiting the RD have rhythmic spontaneous activity in vivo. The RD is known to be critical in controlling firing pattern and regulating the intrinsic status of the neuron (Aizenman and Linden, 1999, Beurrier et al., 1999, Uusiaari et al., 2007). Low-threshold T-type Ca²⁺ currents have been implicated in generation of the RD (Fan et al., 2000, Huguenard, 1996, Viana et al., 1993). Postinhibitory RD in IC neurons has been proposed as an important component to encode particular features of a sound, eg., duration, direction of frequency-modulated sweep, rate of periodic frequency or amplitude modulations and sound gaps (Brand et al., 2000, Casseday et al., 1994, Covey and Casseday, 1999, Ehrlich et al., 1997, Faure et al., 2003, Galazyuk et al., 2005, Large and Crawford, 2002). However, the physiological characteristics of the RD in auditory neurons are largely unknown. In order to understand how the RD of IC neurons contributes to the regulation of a neuron's excitability and its firing, in this study we used the whole-cell patch clamp recording technique to investigate the conditions for generation of the RD. We examined the effects of magnitude and duration of membrane hyperpolarization, the type of ionic current attributable to generation of the RD and physiological features of the RD, including the magnitude, kinetics and time course, in neurons of ICD.

Section snippets

Results

Whole-cell patch clamp recordings were obtained from 82 ICD neurons for the present study. All the neurons displayed sustained firing in response to depolarizing current injections and had a stable resting membrane potential more negative than − 55 mV (range: − 56 to − 64 mV; mean: − 60.3 ± 0.3 mV) throughout the recording.

Discussion

The main results of this study showed that in about half of the ICD neurons sampled a pronounced RD was induced following membrane hyperpolarization. The RD was mediated by Ca²⁺ currents that flowed primarily through low-threshold T-type Ca²⁺ channels. The RD promoted generation of anode break action potentials. The magnitude, kinetics and time course of the RD were closely related to the level and duration of the preceding hyperpolarization. The larger, shorter and faster RD was generated by a

Preparation of brain slices

All procedures in these experiments were performed in compliance with the guidelines of the Canadian Council on Animal Care and were approved by the Carleton University Animal Care Committee. Experimental procedures are detailed in our previous reports (Sun and Wu, 2008). Briefly, Wistar albino rats (10 to 19 days old, Charles River, St. Constant, Quebec, Canada) were decapitated rapidly under anesthesia with isoflurane. The brain was removed and dissected in 24–26 °C artificial cerebral spinal

Acknowledgments

We thank Dr. J.B. Kelly for a critical reading of the manuscript and many helpful suggestions. This work was supported by research grant from Natural Sciences and Engineering Council of Canada (NSERC) to S.H. Wu.

References (71)

AhujaT. et al.
Intrinsic membrane properties and synaptic response characteristics of neurons in the rat's external cortex of the inferior colliculus
Neurosci.
(2007)
AlexanderG.M. et al.
The native T-type calcium current in relay neurons of the primate thalamus
Neurosci.
(2006)
IrfanN. et al.
Synaptic transmission mediated by ionotropic glutamate, glycine and GABA receptors in the rat's ventral nucleus of the lateral lemniscus
Hear. Res.
(2005)
LiY. et al.
In vitro electrophysiology of neurons in subnuclei of rat inferior colliculus
Hear. Res.
(1998)
LoftusW.C. et al.
The cytoarchitecture of the inferior colliculus revisited: A common organization of the lateral cortex in rat and cat
Neurosci.
(2008)
MalmiercaM.S.
The structure and physiology of the rat auditory system: an overview
Internation. Rev. Neurobiol.
(2003)
MalmiercaM.S. et al.
Auditory System
MalmiercaM.S. et al.
Laminar inputs from dorsal cochlear nucleus and ventral cochlear nucleus to the central nucleus of the inferior colliculus: two patterns of convergence
Neurosci.
(2005)
MerchánM.A. et al.
The inferior colliculus of the rat: quantitative immunocytochemical study of GABA and glycine
Neuroci.
(2005)
MitaniA. et al.
Effects of stimulation of the primary auditory cortex upon colliculogeniculate neurons in the inferior colliculus of the cat
Neurosci. Lett.
(1983)

CantN.B.

Projections from the cochlear nuclear complex to the inferior collicuclus

CarboneE. et al.

A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurons

Nature

(1984)

CassedayJ.H. et al.

Neural tuning for sound duration: role of inhibitory mechanisms in the inferior colliculus

Science

(1994)

ChiuT.W. et al.

Basic response determinants of single neurons to amplitude modulation in the auditory midbrain

Exp. Brain Res.

(2000)

CoveyE. et al.

Timing in the auditory system of the bat

Annu. Rev. Physiol.

(1999)

EhretG.

The auditory midbrain, a “shunting yeard” of acoustical information processing

EhretE. et al.

Spectral and intensity coding in the auditory midbrain

EhrlichD. et al.

Neural tuning to sound duration in the inferior colliculus of the big brown bat, Eptesicus fuscus

J. Neurophysiol.

(1997)

FanY.-P. et al.

Biophysical characterization of rat caudal hypothalamic neurons: calcium channel contribution to excitability

J. Neurophysiol.

(2000)

FaureP.A. et al.

Temporal masking reveals properties of sound-evoked inhibition in duration-tuned neurons of the inferior colliculus

J. Neurosci.

(2003)

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Research ReportPhysiological characteristics of postinhibitory rebound depolarization in neurons of the rat's dorsal cortex of the inferior colliculus studied in vitro

Abstract

Introduction

Section snippets

Results

Discussion

Preparation of brain slices

Acknowledgments

Neurosci.

Neurosci.

Hear. Res.

Hear. Res.

Neurosci.

Internation. Rev. Neurobiol.

Neurosci.

Neuroci.

Neurosci. Lett.

Neurosci.

Neurosci.

Neurosci.

Hear. Res.

Neurosci.

Biochem. Biophys. Res. Commun.

Neurosci. Lett.

Neurosci.

Dev. Brain Res.

Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum

J. Neurophysiol.

Hyperpolarization-activated, mixed-cation current (Ih) in octopus cells of the mammalian cochlear nucleus

J. Neurophysiol.

Anatomic, intrinsic, and synaptic properties of dorsal and ventral division neurons in rat medial geniculate body

J. Neurophysiol.

Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode

J. Neurosci.

Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs

J. Neurophsiol.

Duration tuning in the mouse auditory midbrain.J

Neurophysiol.

Projections from the cochlear nuclear complex to the inferior collicuclus

A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurons

Nature

Neural tuning for sound duration: role of inhibitory mechanisms in the inferior colliculus

Science

Basic response determinants of single neurons to amplitude modulation in the auditory midbrain

Exp. Brain Res.

Timing in the auditory system of the bat

Annu. Rev. Physiol.

The auditory midbrain, a “shunting yeard” of acoustical information processing

Spectral and intensity coding in the auditory midbrain

Neural tuning to sound duration in the inferior colliculus of the big brown bat, Eptesicus fuscus

J. Neurophysiol.

Biophysical characterization of rat caudal hypothalamic neurons: calcium channel contribution to excitability

J. Neurophysiol.

Temporal masking reveals properties of sound-evoked inhibition in duration-tuned neurons of the inferior colliculus

J. Neurosci.

Research Report
Physiological characteristics of postinhibitory rebound depolarization in neurons of the rat's dorsal cortex of the inferior colliculus studied in vitro

Hyperpolarization-activated, mixed-cation current (I_h) in octopus cells of the mammalian cochlear nucleus