Synaptic inhibition plays an important role in shaping receptive field (RF) properties in the visual cortex. However, the underlying mechanisms remain not well understood, partly because of difficulties in systematically studying functional properties of cortical inhibitory neurons in vivo. Here, we established two-photon imaging guided cell-attached recordings from genetically labeled inhibitory neurons and nearby "shadowed" excitatory neurons in the primary visual cortex of adult mice. Our results revealed that in layer 2/3, the majority of excitatory neurons exhibited both On and Off spike subfields, with their spatial arrangement varying from being completely segregated to overlapped. In contrast, most layer 4 excitatory neurons exhibited only one discernable subfield. Interestingly, no RF structure with significantly segregated On and Off subfields was observed for layer 2/3 inhibitory neurons of either the fast-spike or regular-spike type. They predominantly possessed overlapped On and Off subfields with a significantly larger size than the excitatory neurons and exhibited much weaker orientation tuning. These results from the mouse visual cortex suggest that different from the push-pull model proposed for simple cells, layer 2/3 simple-type neurons with segregated spike On and Off subfields likely receive spatially overlapped inhibitory On and Off inputs. We propose that the phase-insensitive inhibition can enhance the spatial distinctiveness of On and Off subfields through a gain control mechanism.

Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development1-4. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested, due to the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. In this study, in vivo whole-cell voltage-clamp recordings were applied to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency-intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. To our surprise, co-tuned excitation and inhibition were observed right after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relative strong feedforward inhibition is formed independent of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days after the hearing onset and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in a relatively broader inhibitory tuning in adult A1 neurons. Thus, the development of cortical synaptic TRFs after hearing onset is marked by a slight breakdown of priorly formed excitation-inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.

Intensity-tuned neurons, characterized by their nonmonotonic response-level function, may play important roles in the encoding of sound intensity-related information. The synaptic mechanisms underlying intensity tuning remain unclear. Here, in vivo whole-cell recordings in rat auditory cortex revealed that intensity-tuned neurons, mostly clustered in a posterior zone, receive imbalanced tone-evoked excitatory and inhibitory synaptic inputs. Excitatory inputs exhibit nonmonotonic intensity tuning, whereas with tone intensity increments, the temporally delayed inhibitory inputs increase monotonically in strength. In addition, this delay reduces with the increase of intensity, resulting in an enhanced suppression of excitation at high intensities and a significant sharpening of intensity tuning. In contrast, non-intensity-tuned neurons exhibit covaried excitatory and inhibitory inputs, and the relative time interval between them is stable with intensity increments, resulting in monotonic response-level function. Thus, cortical intensity tuning is primarily determined by excitatory inputs and shaped by cortical inhibition through a dynamic control of excitatory and inhibitory timing.

Synaptic inputs underlying spike receptive fields (RFs) are key to understanding mechanisms for neuronal processing. Here, whole-cell voltage-clamp recordings from neurons in mouse primary visual cortex revealed the spatial patterns of their excitatory and inhibitory synaptic inputs evoked by On and Off stimuli. Surprisingly, neurons with either segregated or overlapped On/Off spike subfields exhibited substantial overlaps between all the four synaptic subfields. The segregated RF structures are generated by the integration of excitation and inhibition with a stereotypic pattern: the peaks of excitatory On/Off subfields are separated and flank co-localized peaks of inhibitory On/Off subfields. The small mismatch of excitation/inhibition leads to an asymmetric inhibitory shaping of On/Off spatial tunings, resulting in a great enhancement of their distinctiveness. Thus, slightly separated On/Off excitation together with intervening inhibition can create simple-cell RF structure, and the dichotomy of RF structures may arise from a fine-tuning of the spatial arrangement of synaptic inputs.

Abstract. We present consistent annual mean atmospheric histories and growth rates for the mainly anthropogenic halogenated compounds HCFC-22, HCFC-141b, HCFC-142b, HFC-134a, HFC-125, HFC-23, PFC-14 and PFC-116, which are all potentially useful oceanic transient tracers (tracers of water transport within the ocean), for the Northern and Southern Hemisphere with the aim of providing input histories of these compounds for the equilibrium between the atmosphere and surface ocean. We use observations of these halogenated compounds made by the Advanced Global Atmospheric Gases Experiment (AGAGE), the Scripps Institution of Oceanography (SIO), the Commonwealth Scientific and Industrial Research Organization (CSIRO), the National Oceanic and Atmospheric Administration (NOAA) and the University of East Anglia (UEA). Prior to the direct observational record, we use archived air measurements, firn air measurements and published model calculations to estimate the atmospheric mole fraction histories. The results show that the atmospheric mole fractions for each species, except HCFC-141b and HCFC-142b, have been increasing since they were initially produced. Recently, the atmospheric growth rates have been decreasing for the HCFCs (HCFC-22, HCFC-141b and HCFC-142b), increasing for the HFCs (HFC-134a, HFC-125, HFC-23) and stable with little fluctuation for the PFCs (PFC-14 and PFC-116) investigated here. The atmospheric histories (source functions) and natural background mole fractions show that HCFC-22, HCFC-141b, HCFC-142b, HFC-134a, HFC-125 and HFC-23 have the potential to be oceanic transient tracers for the next few decades only because of the recently imposed bans on production and consumption. When the atmospheric histories of the compounds are not monotonically changing, the equilibrium atmospheric mole fraction (and ultimately the age associated with that mole fraction) calculated from their concentration in the ocean is not unique, reducing their potential as transient tracers. Moreover, HFCs have potential to be oceanic transient tracers for a longer period in the future than HCFCs as the growth rates of HFCs are increasing and those of HCFCs are decreasing in the background atmosphere. PFC-14 and PFC-116, however, have the potential to be tracers for longer periods into the future due to their extremely long lifetimes, steady atmospheric growth rates and no explicit ban on their emissions. In this work, we also derive solubility functions for HCFC-22, HCFC-141b, HCFC-142b, HFC-134a, HFC-125, HFC-23, PFC-14 and PFC-116 in water and seawater to facilitate their use as oceanic transient tracers. These functions are based on the Clark–Glew–Weiss (CGW) water solubility function fit and salting-out coefficients estimated by the poly-parameter linear free-energy relationships (pp-LFERs). Here we also provide three methods of seawater solubility estimation for more compounds. Even though our intention is for application in oceanic research, the work described in this paper is potentially useful for tracer studies in a wide range of natural waters, including freshwater and saline lakes, and, for the more stable compounds, groundwaters.