Intrinsic Cortical Signal Gain

Abstract

The role of the cortex in receiving incoming sensory information provided by thalamic inputs is not completely understood. Is the cortex act a passive receiving system, performing subsequent manipulations on a similar copy of the incoming data, or does it actively transform thalamic input to improve performance or detection? In a recent study, Li et al (Intracortical multiplication of thalamocortical signals in mouse auditory cortex. Nat Neurosci. 2013;16(9):1179-1181) used an optogenetics technique to support the latter interpretation. The authors dampened intracortical circuitry by activating parvalbumin (PV+) expressing inhibitory neurons locally, and found that in the uninhibited state, primary auditory cortex amplifies thalamocortical responses while leaving the spectral tuning curves preserved. This process appears to increase the duration and gain of thalamic input signals and serves to improve the signal-to-noise properties of the transmitted information. The authors performed this study in anesthetized mice, examining specifically primary auditory cortex (A1). Using blue LED illumination, they activated the PV+ inhibitory cellular component which had been modified (Cre-loxP recombination using an adeno-associated viral vector) to express channelrhodopsin-2 (ChR2). The PV+ neurons increased their firing rates considerably with illumination. Extracellular multi-unit recordings were performed in A1 for tonotopic mapping, with tone inputs applied to the contralateral ear. Similar recordings were also performed stereotactically in the ventral medial geniculate body (MGBv) in a tonotopic fashion, and loose-patch and whole-cell voltage clamp recordings were made from the Layer IV region of A1 (predominantly pyramidal cells). During optogenetic silencing, the authors found that the cortical response produced by equivalent thalamic inputs (for the same frequency tone stimulus) was reduced by a factor of 2.4 as compared to the normal non-silenced state. Additionally, the time duration of the cortical response was reduced during optogenetic silencing. The response amplification produced by the surrounding cortical input appeared additionally to preserve the preferred cortical response to upward going frequency-modulated sweeps, but the overall amplitude change brought on by optogenetic silencing was independent of direction of frequency sweeps. The onset latencies to sweep inputs remained unchanged between the silenced and non-silenced state, implying that the spectral range of the cortical response is determined by the thalamocortical input component, and not modulated by surrounding cortical input. In summary, Li et al describe an optogenetic method for silencing surrounding cortical influences on sensory input transmission to the primary auditory cortex of mice. The authors found amplification of the thalamic auditory signal input brought on by surrounding cortical input, which preserves the cortical frequency tuning response and appears to increase the signal-to-noise properties of the incoming MGBv relayed signal. This paper has relevance to the neurosurgeon or engineer interested in neuroprosthetic development. It may be possible to mimic this type of cortical pre-processing to amplify and augment incoming sensory information in future prosthetic systems that rely on sensory input as a feedback mechanism.Figure: A and C, 2 neurons exhibiting frequency Sdependent tone evoked responses, both during the case of optogenetic silencing of the cortical network (lower traces) and during the non-silenced case (upper traces). B and D, linear nature of pink amplitude of thalamic input vs the total excitation evoked by the same tone stimulus (left subplot). Onset latencies of the thalamocortical (blue) and total cortical (red) excitatory responses at different frequencies (right subplot). (Reprinted by permission from Macmillan Publishers Ltd: Li LY, Li YT, Zhou M, Tao HW, Zhang LI. Intracortical multiplication of thalamocortical signals in mouse auditory cortex. Nat Neurosci. 2013;16(9):1179-1181).