GABAA receptor binding in the aging rat inferior colliculus

Milbrandt, Joseph C.; Albin, Roger L.; Turgeon, Sarah M.; Caspary, Donald M.

doi:10.1016/0306-4522(96)00050-4

Cited by 73 publications

(42 citation statements)

References 64 publications

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“…As mentioned above, selectivity of IC neurons to temporal features of sound depends critically on a balanced interplay of excitation and inhibition. In line with our results, a severe downregulation of the inhibitory transmitter system has been reported for the aged auditory system (Banay-Schwartz et al, 1989;Milbrandt et al, 1994Milbrandt et al, , 1996Milbrandt et al, , 2000Willott et al, 1997). Studies of monkey primary visual cortex showed, in accordance with our results, a decreased orientation and direction selectivity of single neurons and orientation selectivity of single neurons to be reinstalled by GABA application (Schmolesky et al, 2000;Leventhal et al, 2003).…”

Section: Implications For Temporal Processingsupporting

confidence: 92%

“…In aged animals, presynaptic and postsynaptic levels of the inhibitory neurotransmitters glycine and GABA and their respective receptors are significantly reduced (Banay-Schwartz et al, 1989;Milbrandt et al, 1994Milbrandt et al, , 1996Milbrandt et al, , 1997Milbrandt et al, , 2000Willott et al, 1997;Krenning et al, 1998;Burianova et al, 2009), potentially disrupting the balance of excitation and inhibition.…”

Section: Introductionmentioning

confidence: 99%

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Impaired Auditory Temporal Selectivity in the Inferior Colliculus of Aged Mongolian Gerbils

Khouri

Lesica

Grothe

2011

Journal of Neuroscience

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Aged humans show severe difficulties in temporal auditory processing tasks (e.g., speech recognition in noise, low-frequency sound localization, gap detection). A degradation of auditory function with age is also evident in experimental animals. To investigate agerelated changes in temporal processing, we compared extracellular responses to temporally variable pulse trains and human speech in the inferior colliculus of young adult (3 month) and aged (3 years) Mongolian gerbils. We observed a significant decrease of selectivity to the pulsetrainsinneuronalresponsesfromagedanimals.Thisdecreaseinselectivityled,onthepopulationlevel,toanincreaseinsignalcorrelations and therefore a decrease in heterogeneity of temporal receptive fields and a decreased efficiency in encoding of speech signals. A decrease in selectivity to temporal modulations is consistent with a downregulation of the inhibitory transmitter system in aged animals. These alterations in temporal processing could underlie declines in the aging auditory system, which are unrelated to peripheral hearing loss. These declines cannot be compensated by traditional hearing aids (that rely on amplification of sound) but may rather require pharmacological treatment.

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Section: Implications For Temporal Processingsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Impaired Auditory Temporal Selectivity in the Inferior Colliculus of Aged Mongolian Gerbils

Khouri

Lesica

Grothe

2011

Journal of Neuroscience

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“…GABA levels, GABA immunostaining, GAD activity and GABA A and GABA B receptor binding all decrease in the aged rodent IC (BanaySchwartz et al, 1989a; Banay-Schwartz et al, 1989b; Caspary et al., 1990; Gutiérrez et al, 1994;Raza et al, 1994;Milbrandt et al, 1994;Milbrandt et al, 1996). The IC neuropil shows an age-related rearrangement of synaptic endings onto soma and proximal dendrites (Helfert et al, 1999).…”

Section: Age-related Changes In Inferior Colliculusmentioning

confidence: 99%

“…Localization of sounds in the horizontal plane is necessary to avoid predation or to successfully localize prey. Localization of high , 1975; Caspary et al, 1990; Gutiérrez et al, 1994;Milbrandt et al, 1994;Raza et al, 1994;Milbrandt et al, 2000) Postsynaptic Altered GABA A receptor subunit composition and quantitative receptor binding (Gutiérrez et al, 1994;Milbrandt et al, 1996; Caspary et al, 1999) Inferior colliculus THE JOURNAL OF EXPERIMENTAL BIOLOGY 1784 frequency sounds is thought to involve left vs right comparison of interaural intensity differences, which primarily occurs in the LSO (Batra et al, 1997;Tollin and Yin, 2002). Neurons that compare low frequency sounds from both sides of the head are mostly located in the MSO.…”

mentioning

confidence: 99%

Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system

Caspary

Ling

Turner

et al. 2008

Journal of Experimental Biology

421

353

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SummaryAging and acoustic trauma may result in partial peripheral deafferentation in the central auditory pathway of the mammalian brain. In accord with homeostatic plasticity, loss of sensory input results in a change in pre-and postsynaptic GABAergic and glycinergic inhibitory neurotransmission. As seen in development, age-related changes may be activity dependent. Age-related presynaptic changes in the cochlear nucleus include reduced glycine levels, while in the auditory midbrain and cortex, GABA synthesis and release are altered. Presumably, in response to age-related decreases in presynaptic release of inhibitory neurotransmitters, there are age-related postsynaptic subunit changes in the composition of the glycine (GlyR) and GABA A (GABA A R) receptors. Age-related changes in the subunit makeup of inhibitory pentameric receptor constructs result in altered pharmacological and physiological responses consistent with a net down-regulation of functional inhibition. Age-related functional changes associated with glycine neurotransmission in dorsal cochlear nucleus (DCN) include altered intensity and temporal coding by DCN projection neurons. Loss of synaptic inhibition in the superior olivary complex (SOC) and the inferior colliculus (IC) likely affect the ability of aged animals to localize sounds in their natural environment. Age-related postsynaptic GABA A R changes in IC and primary auditory cortex (A1) involve changes in the subunit makeup of GABA A Rs. In turn, these changes cause age-related changes in the pharmacology and response properties of neurons in IC and A1 circuits, which collectively may affect temporal processing and response reliability. Findings of age-related inhibitory changes within mammalian auditory circuits are similar to age and deafferentation plasticity changes observed in other sensory systems. Although few studies have examined sensory aging in the wild, these age-related changes would likely compromise an animal's ability to avoid predation or to be a successful predator in their natural environment.Key words: aging, central auditory system, GABA A receptor, glycine receptor, inhibitory neurotransmission, plasticity. THE JOURNAL OF EXPERIMENTAL BIOLOGY 1782important in determining the location of sound, echolocation and extracting information from voiced and unvoiced communication signals (Carr et al., 1986;Portfors and Wenstrup, 2001).The complex processing that occurs at the level of the MGB and the A1 is beyond the scope of the present review. Coding in the auditory cortex has been recently reviewed (Wang, 2007;Rauschecker, 2005). As seen in the visual cortex, in the auditory cortex, acoustically complex hierarchical analysis has been described for awake-behaving primates (Rauschecker, 2005;Steinschneider et al., 2008). A1 has been shown to undergo agerelated plastic changes, including down-regulation of inhibitory coding, similar to that observed at lower levels of the auditory pathway and in visual cortex. Similar to age-related changes, activity-dependant changes have be...

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“…Loss of central inhibition would be expected to significantly alter auditory processing (Brozoski et al 2002;Caspary et al 1999;Suneja et al 1998a;Szczepaniak and Moller 1996;Willott and Lu 1982), which, in turn, could lead to inappropriate neuroplastic changes eventually expressed as a sensation of tinnitus. Because g-amino butyric acid (GABA) is a generally inhibitory neurotransmitter found in appreciable amounts at many levels of the central auditory pathway (Backoff et al 1997;Bauer et al 2000;Caspary et al 1995;Milbrandt et al 1996;Suneja et al 1998b), a corollary to the loss-of-inhibition and tinnitus hypothesis would be the down-regulation of GABA activity. If the linkage is causal, then elevating GABA function in animals demonstrated to have tinnitus should reduce their tinnitus.…”

Section: Introductionmentioning

confidence: 99%

Vigabatrin, a GABA Transaminase Inhibitor, Reversibly Eliminates Tinnitus in an Animal Model

Brozoski

Spires

Bauer

2007

JARO

110

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Animal models have facilitated basic neuroscience research investigating the pathophysiology of tinnitus. It has been hypothesized that partial deafferentation produces a loss of tonic inhibition in the auditory system that may lead to inappropriate neuroplastic changes eventually expressed as tinnitus. The pathological down-regulation of g-amino butyric acid (GABA) provides a potential mechanism for this loss of inhibition. Using an animal model previously demonstrated to be sensitive to treatments that either induce or attenuate tinnitus, the present study examined the effect of the specific GABA agonist vigabatrin on chronic tinnitus. It was hypothesized that vigabatrin would decrease the evidence of tinnitus by restoring central inhibitory function through increased GABA availability. Vigabatrin has been demonstrated to elevate central GABA levels (Mattson et al. 1995). Tinnitus was induced in rats using a single 1-h unilateral exposure to band-limited noise, which preserved normal hearing in one ear. Psychophysical evidence of tinnitus was obtained using a free-operant conditioned-suppression method: Rats lever-pressed for food pellets and were trained to discriminate between the presence and absence of sound by punishing lever pressing with a mild foot shock (0.5 mA; 1 s) at the conclusion of randomly introduced silent periods (60 s) inserted into background low-level noise. Additional random insertion of pure tone and noise periods of variable intensity enabled the derivation of psychophysical functions that reflected the presence of tinnitus with features similar to 20-kHz tones. Vigabatrin was chronically administered via drinking water at 30 and 81 mg kg _ 1 day _ 1, with each dose level tested over 2 weeks, followed by a 0-mg washout test. Vigabatrin completely and reversibly eliminated the psychophysical evidence of tinnitus at both doses. Although vigabatrin has serious negative side effects that have prevented its clinical use in the USA, it is nevertheless a potentially useful tool in unraveling tinnitus pathophysiology.

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GABAA receptor binding in the aging rat inferior colliculus

Cited by 73 publications

References 64 publications

Impaired Auditory Temporal Selectivity in the Inferior Colliculus of Aged Mongolian Gerbils

Impaired Auditory Temporal Selectivity in the Inferior Colliculus of Aged Mongolian Gerbils

Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system

Vigabatrin, a GABA Transaminase Inhibitor, Reversibly Eliminates Tinnitus in an Animal Model

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