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Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

ABSTRACT: In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

SUBMITTER: Anderson CT

PROVIDER: S-EPMC5876454 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

Anderson Charles T CT Kumar Manoj M Xiong Shanshan S Tzounopoulos Thanos T

eLife 20170909

In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary au ...[more]

PMID: 28887876

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Project description:The mammalian cerebral cortex is a dense network composed of local, subcortical, and intercortical synaptic connections. As a result, mapping cell type-specific neuronal connectivity in the cerebral cortex in vivo has long been a challenge for neurobiologists. In particular, the development of excitatory and inhibitory interneuron presynaptic input has been hard to capture. We set out to analyze the development of this connectivity in the first postnatal month using a murine model. First, we surveyed the connectivity of one of the earliest populations of neurons in the brain, the Cajal-Retzius (CR) cells in the neocortex, which are known to be critical for cortical layer formation and are hypothesized to be important in the establishment of early cortical networks. We found that CR cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We also found that both excitatory pyramidal neurons and inhibitory interneurons received broad inputs in the first postnatal week, including inputs from CR cells. Expanding our analysis into the more mature brain, we assessed the inputs onto inhibitory interneurons and excitatory projection neurons, labeling neuronal progenitors with Cre drivers to study discrete populations of neurons in older cortex, and found that excitatory cortical and subcortical inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period. Cell type-specific circuit mapping is specific, reliable, and effective, and can be used on molecularly defined subtypes to determine connectivity in the cortex.Significance statementMapping cortical connectivity in the developing mammalian brain has been an intractable problem, in part because it has not been possible to analyze connectivity with cell subtype precision. Our study systematically targets the presynaptic connections of discrete neuronal subtypes in both the mature and developing cerebral cortex. We analyzed the connections that Cajal-Retzius cells make and receive, and found that these cells receive inputs from deeper-layer excitatory neurons and inhibitory interneurons in the first postnatal week. We assessed the inputs onto inhibitory interneurons and excitatory projection neurons, the major two types of neurons in the cortex, and found that excitatory inputs are refined by the fourth week of development, whereas local inhibitory inputs increase during this postnatal period.

Dataset Information

Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

Publications

Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

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