Distinct neural firing mechanisms to tonal stimuli offset in the inferior colliculus of mice in vivo.
ABSTRACT Offset neurons, which fire at the termination of sound, likely encode sound duration and serve to process temporal information. Offset neurons are found in most ascending auditory nuclei; however, the neural mechanisms that evoke offset responses are not well understood. In this study, we examined offset neural responses to tonal stimuli in the inferior colliculus (IC) in vivo with extracellular and intracellular recording techniques in mice. Based on peristimulus time histogram (PSTH) patterns, we classified extracellular offset responses into four types: Offset, Onset-Offset, Onset-Sustained-Offset and Inhibition-Offset types. Moreover, using in vivo whole-cell recording techniques, we found that offset responses were generated in most cells through the excitatory and inhibitory synaptic inputs. However, in a small number of cells, the offset responses were generated as a rebound to hyperpolarization during tonal stimulation. Many offset neurons fired robustly at a preferred duration of tonal stimulus, which corresponded with the timing of rich excitatory synaptic inputs. We concluded that most IC offset neurons encode the termination of the tone stimulus by responding to inherited ascending synaptic information, which is tuned to sound duration. The remainder generates offset spikes de novo through a post-inhibitory rebound mechanism.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: Pharmacological block of inhibition is often used to determine if inhibition contributes to spike selectivity, in which a preferred stimulus evokes more spikes than a null stimulus. When inhibitory block reduces spike selectivity, a common interpretation is that differences between the preferred- and null-evoked inhibitions created the selectivity from less-selective excitatory inputs. In models based on empirical properties of cells from the inferior colliculus (IC) of awake bats, we show that inhibitory differences are not required. Instead, inhibition can enhance spike selectivity by changing the gain, the ratio of output spikes to input current. Within the model, we made preferred stimuli that evoked more spikes than null stimuli using five distinct synaptic mechanisms. In two cases, synaptic selectivity (the differences between the preferred and null inputs) was entirely excitatory, and in two it was entirely inhibitory. In each case, blocking inhibition eliminated spike selectivity. Thus, observing spike rates following inhibitory block did not distinguish among the cases where synaptic selectivity was entirely excitatory or inhibitory. We then did the same modeling experiment using empirical synaptic conductances derived from responses to preferred and null sounds. In most cases, inhibition in the model enhanced spike selectivity mainly by gain modulation and firing rate reduction. Sometimes, inhibition reduced the null gain to zero, eliminating null-evoked spikes. In some cases, inhibition increased the preferred gain more than the null gain, enhancing the difference between the preferred- and null-evoked spikes. Finally, inhibition kept firing rates low. When selectivity is quantified by the selectivity index (SI, the ratio of the difference to the sum of the spikes evoked by the preferred and null stimuli), inhibitory block reduced the SI by increasing overall firing rates. These results are consistent with inhibition shaping spike selectivity by gain control.Frontiers in Neural Circuits 01/2012; 6:67. · 3.33 Impact Factor
Distinct neural firing mechanisms to tonal stimuli offset in the
inferior colliculus of mice in vivo.
Author(s)Kasai, Masatoshi; Ono, Munenori; Ohmori, Harunori
CitationNeuroscience research (2012), 73(3): 224-237
© 2012 Elsevier Ireland Ltd and the Japan Neuroscience
KURENAI : Kyoto University Research Information Repository
Distinct Neural Firing Mechanisms to Tonal Stimuli Offset in the Inferior Colliculus of
Mice in vivo
Masatoshi KASAI*1, Munenori ONO, Harunori OHMORI
Department of Neurobiology, Kyoto University Graduate School of Medicine, Kyoto,
MK: email@example.com, firstname.lastname@example.org
*To whom correspondence should be addressed;
Offset neurons, which fire at the termination of sound, likely encode sound duration
and serve to process temporal information. Offset neurons are found in most ascending
auditory nuclei; however, the neural mechanisms that evoke offset responses are not well
understood. In this study, we examined offset neural responses to tonal stimuli in the
inferior colliculus (IC) in vivo with extracellular and intracellular recording techniques in
mice. Based on peristimulus time histogram (PSTH) patterns, we classified extracellular
offset responses into four types; Offset, Onset-Offset, Onset-Sustained-Offset and
Inhibition-Offset types. Moreover, using in vivo whole-cell recording techniques, we found
that offset responses were generated in most cells through the excitatory and inhibitory
synaptic inputs. However, in a small number of cells, the offset responses were generated as
1 Present Adress: Department of Developmental Physiology, National Institute for Physiological
Sciences, Okazaki, Japan.
a rebound to hyperpolarization during tonal stimulation. Many offset neurons fired robustly
at a preferred duration of tonal stimulus, which corresponded with the timing of rich
excitatory synaptic inputs. We concluded that most IC offset neurons encode the termination
of the tone stimulus by responding to inherited ascending synaptic information, which is
tuned to sound duration. The remainder generates offset spikes de novo through a post-
inhibitory rebound mechanism.
IC neurons respond to tonal duration and fire at the offset in four patterns.
Timing and balance between EPSC and IPSC determined the pattern of offset firings.
Some neurons fire from the rebound depolarization to tone induced inhibitory inputs.
Charge carried by offset synaptic inputs was largest at the preferred tonal duration.
Audition, Inferior Colliculus, Whole-cell Recording, Offset Response, Duration Tuning,
We appreciate Prof. Tom C.T. Yin (Department of Neuroscience, UW-Madison
School of Medicine and Public Health) for reading the manuscript and providing helpful
comments, Prof. Y. Yanagawa (Department of Genetic and Behavioral Neuroscience,
Gunma University Graduate School of Medicine) for providing GAD67-GFP knock-in
mice, and Prof. T. Kaneko and Dr. K. Nakamura (Department of Morphological Brain
Science, Graduate School of Medicine, Kyoto University) for the generous gift of the anti-
Natural sounds have several features, such as frequency, level, duration and timing,
and these features provide abundant information for animal communication. Inferior
colliculus (IC) is believed to be the first integrative center for processing complex sounds
because all sound information converges in this brain region. Synaptic inputs from the
unilateral and bilateral lower auditory nuclei, as well as the descending projections from the
auditory cortices, all converge in this region (reviewed in Casseday and Covey 1996). As a
result, IC neurons show a variety of firing patterns that represent various types of auditory
information (Ehret and Moffat 1985; Knudsen and Konishi 1978; Toronchuk et al. 1992;
Casseday et al. 1994; Wang et al. 2006). Sound duration is thought to be one of the essential
information for auditory processing and complex cognitive function. To represent sound
duration, certain neurons fire continuously during the stimulus, and other neurons fire at the
stimulus offset to encode its termination. The neurons that encode the termination of sound
are called offset neurons. These neurons are found in the IC (bat: Casseday et al. 1994;
Voytenko and Galazyuk 2008; rodent: Brand et al. 2000; Pérez-González et al. 2006; cat:
Radionova 1988) as well as in other auditory nuclei (cochlear nucleus, Young and Brownell
1976; superior olivary nuclei, Covey et al. 1991; Grothe 1994; Kuwada and Batra 1999;
Behrend et al. 2002; Kulesza et al. 2003; nuclei of lateral lemniscus, Covey and Casseday
1991; medial geniculate body, He 2001; auditory cortex, Recanzone 2000; Scholl et al.
2010). Recently, the offset firing mechanism in superior paraolivary nucleus (SPON) was
proposed to be due to a disinhibition mechanism (Kulesza et al. 2007). Moreover, post-
inhibitory rebound firing facilitates the preciseness of the offset responses (Felix et al. 2011;
Kopp-Scheinpflug et al. 2011). A convergence of post-inhibitory rebound and delayed
excitatory inputs has been suggested to create offset firing in duration-sensitive neurons in
the IC (Casseday et al. 1994; Mora and Kössl 2004; Faure et al. 2003). Computational
models have also been proposed for mechanisms that create fine duration selectivity (Aubie
et al. 2009). Recent in vivo whole-cell recordings in the IC demonstrated the presence of
offset spikes in bats and mice (Xie et al. 2007; Tan and Borst 2007); however, detailed
offset firing mechanisms have not been determined. In this paper, we conducted in vivo
recordings from offset neurons in the IC extracellularly and intracellularly in mice, and we
found that offset firing is generated by at least two distinct neural mechanisms; specifically,
one is a rebound firing that is induced by membrane hyperpolarization during tone and the
other is the firing that is induced through direct excitatory synaptic inputs at the tonal offset.
2. Materials and methods
2.1 Animal preparations
Experimental procedures conformed to guiding principles for the care and use of
animals in the field of physiological sciences set by the Japanese Physiological Society. ICR
mice (Shimizu; Kyoto, Japan) were used in most experiments, and in some cases, mice
expressing green fluorescent protein (GFP) under the control of glutamate decarboxylase 67
(GAD67) were used in combination with juxtacellular staining to identify GABAergic
neurons (GAD67-GFP knock-in mice; Yanagawa et al. 2001; Tamamaki et al. 2003).
Animals of 4 to 12 weeks old were anesthetized with either chloral hydrate (intraperitoneal
(i.p.) injection, 0.4 g/kg) or urethane (i.p. injection, 1.7 g/kg). Pinching the foot or tail
almost every 30 minutes tested the anesthetic condition of the animal. When pinching reflex
appeared, we added additional dose to maintain the level of anesthesia. We could not find
particular difference in firing properties of IC offset neurons between these two anesthetics,
in responses to tonal stimuli as well as in patterns of spontaneous firings; therefore we
accumulated data from all offset neurons in the following analyses. The animals were
mounted on a modified stereotaxic instrument (Narishige; Tokyo, Japan), and body
temperature was maintained throughout the experiments using a warming pad. A plastic
plate was fastened on the nasal bone to immobilize the head with dental cement (Fuji
Ionomer Type II: GC; Tokyo, Japan), and a pair of hollow ear bars was attached to the
opening of the ear canal. The unilateral surface of IC was exposed by removing a piece of
the inter parietal bone and dura mater beneath it. Agarose gel (Agarose-LGT, Nacalai;
Kyoto, Japan; 2–4% in a saline containing (in mM): 130 NaCl, 4.5 KCl, 2 CaCl2, 5 PIPES-
Na (pH 7.3) and 6% glucose) was placed on the exposed IC to prevent the surface from
pulsating and drying.
2.2 Auditory stimulation
Tone stimuli were generated by a digital audio board (SE-200PCI, Onkyo; Tokyo,
Japan) and were presented monaurally through the ear bar by a pair of tweeters (SRH291,
Clarion; Saitama, Japan). The tones were in 30 steps of logarithmic-spaced frequencies that
ranged from 1.7 kHz to 72 kHz at 10 different sound pressure levels (0–90 dBSPL in 10 dB