GABAergic inhibition shapes SAM responses in rat auditory thalamus

Abstract

Auditory thalamus (medial geniculate body [MGB]) receives ascending inhibitory GABAergic inputs from inferior colliculus (IC) and descending GABAergic projections from thalamic reticular nucleus (TRN) with both inputs postulated to play a role in shaping temporal responses. Previous studies suggested that enhanced processing of temporally rich stimuli occurs at the level of MGB, with our recent study demonstrating enhanced GABA sensitivity in MGB compared to IC. The present study used sinusoidal amplitude modulated (SAM) stimuli to generate modulation transfer functions (MTFs), to examine the role of GABAergic inhibition in shaping the response properties of MGB single units in anesthetized rats. Rate MTFs (rMTFs) were parsed into “bandpass (BP)”, “mixed (Mixed)”, “highpass (HP)” or “atypical” response types, with most units showing the Mixed response type. GABAA receptor blockade with iontophoretic application of the GABAA receptor (GABAAR) antagonist gabazine (GBZ) selectively altered the response properties of most MGB neurons examined. Mixed and HP units showed significant GABAAR mediated SAM evoked rate response changes at higher modulation frequencies (fms), which were also altered by NMDA receptor blockade (2R)-amino-5-phosphonopentanoate (AP5). Bandpass units, and the lower arm of Mixed units responded to GABAAR blockade with increased responses to SAM stimuli at or near the rate best modulation frequency (rBMF). The ability of GABA circuits to shape responses at higher modulation frequencies is an emergent property of MGB units, not observed at lower levels of the auditory pathway and may reflect activation of MGB NMDA receptors (Rabang and Bartlett, 2011, Rabang et al., 2012). Together, GABAARs exert selective rate control over selected fms, generally without changing the units’ response type. These results showed that coding of modulated stimuli at the level of auditory thalamus is at least, in part, strongly controlled by GABA neurotransmission, in delicate balance with glutamatergic neurotransmission.

Top‐down or bottom up: decreased stimulus salience increases responses to predictable stimuli of auditory thalamic neurons

“…Units CFs and BFs ranged between 2 and 32 kHz. Similar to studies reported by Bartlett andWang (2007, 2011) and Cai et al (2014Cai et al ( , 2015, SAM responses, based on rMTF shape across f m , conformed to previously described band-pass, high-pass, low-pass, mixed (most common) or atypical types. BMFs ranged between 8 and 512 Hz, congruent with the rMTF profile types described above.…”

“…Anaesthesia was then maintained with i.p. injections of 100% urethane (initially 1.3 mL kg -1 , then booster doses at one-third of the initial dose; Sigma-Aldrich) (Cai et al 2014;Cai & Caspary, 2015). Rats were placed in a modified (no ear bars) stereotaxic frame in an IAC sound-attenuating booth (Industrial Acoustic Co., Inc., New York, NY, USA) with the body temperature maintained at 37 ± 0.5°C using a thermostatically controlled heating blanket.…”

“…Calibration tables in dB sound pressure level (SPL) were used to set programmable attenuators (PA5; Tucker Davis Technologies) to achieve pure tone levels accurate within 2 dB SPL for frequencies up to 45 kHz. Response maps were used to determine the characteristic frequency (CF) of sorted single units (Cai & Caspary, 2015). Random tone-burst stimuli (duration of 50 ms, 4 ms rise/fall time, 2 Hz rate) were presented in 0.10 to 0.25 octave frequency steps (1-32 KHz) in 10 dB SPL steps (0-80 dB) to determine the response maps.…”

Ageing affects dual encoding of periodicity and envelope shape in rat inferior colliculus neurons

“…Neural inhibition has also been shown to be crucial for shaping neural activity elicited by amplitude-modulated sounds (Yang & Pollak, 1997;Backoff et al, 1999;Cai & Caspary, 2015; but see also Caspary et al, 2002;Zhang & Kelly, 2003). Yet, the direction in which a reduction in neural inhibition affects neural synchronisation is not clear.…”

Auditory thalamic circuits and GABAA receptor function: Putative mechanisms in tinnitus pathology

“…It shapes input/output functions, alters frequency tuning, and sharpens temporal response accuracy while gating neurotransmission to auditory cortex (AI) (Bartlett, 2013; Edeline, 2011; Llano et al, 2000; Richardson et al, 2012; Wang et al, 2008). In vivo and in vitro electrophysiological findings suggest distinct properties of inhibitory neurotransmission in the MGB relative to other ascending auditory structures, such as inferior colliculus (IC) (Cai et al, 2015; Cai et al, 2013; Richardson et al, 2011). The rat MGB contains relatively few GABAergic interneurons, but there are substantial GABAergic inhibitory projections from inferior colliculus and from the thalamic reticular nucleus (Bartlett et al, 2000; Peruzzi et al, 1997; Saint Marie et al, 1997b; Winer et al, 1988; Winer et al, 1996a; Winer et al, 1996b).…”