Galanin Enhances the Responses of Neurons in Primary Auditory Cortex

甘丙肽對初級聽皮層細胞反應的增強作用研究

Student thesis: Doctoral Thesis

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Award date2 Sep 2019

Abstract

Our lab previously discovered that visuoauditory conditioning resulted in the transient responses of neurons in the primary auditory cortex (AC1) to visual stimuli. Formation of this visuoauditory association can be suppressed by either inactivation of the medial prefrontal cortex (mPFC) or local infusion of a galanin antagonist into the AC1. Electrical activation of the mPFC in anesthetized rats induces a transient amplification of the neuronal responses in the AC1, but many experiments suggest that the mPFC can modulate AC1 activity, and galanin biding sites are found across the neuro-cortex. Based on these observations, we assumed that the mPFC modulates AC1 activities through galanin-mediated enhancement of neuronal firing.

We first performed experiments to identify projections from the mPFC to the AC1 and found that there are galanin-containing galanin neurons in the mPFC that project directly to the AC1. We also showed that galanin co-existed with both gamma-Aminobutyric acid (GABA) and glutamate in the mPFC.

To test the effect of galanin and its antagonist M40 on neuron activity, these drugs were injected into the primary AC1. Galanin enhanced neuronal responses to noise stimulations, while M40 blocked this enhancement. The concentrations with the most significant effect were used in subsequent behavioral experiments. Artificial cerebrospinal fluid (ACSF) was used as the vehicle control.

An auditory discrimination task was performed to test the influence of galanin and its antagonist on freely behaving animals. We adopted a behavioral apparatus with three holes. Rats with bilateral implantations of electrodes and guiding cannula combined arrays in both hemispheres of the AC1 were trained to approach the left- or right-most hole of the apparatus to retrieve a reward depending on whether the right or left AC1 was electrically stimulated. After training, the rat was able to perform the task with an accuracy of nearly 100%. Current intensity was tuned to adjust rat performance to a correct rate of ~70%, and we assessed whether galanin infusion into one hemisphere increased the correct rate of reward retrieval from the contralateral hole. In a different session, we set the baseline performance to a correct rate of ~80% and found that M40 infusion decreased performance accuracy. ACSF was used as the vehicle control to ensure that changes in the correct rate were correlated with galanin or M40 administration.

After we characterized galanin-mediated enhancement on the evoked responses of auditory neurons, we used Gal-CRE mice to manipulate galanin release by galanin-positive neurons projecting from the mPFC to AC1. Gal-CRE mice with bilateral implantation of optical fiber and guiding cannula combined arrays in both AC1 were trained to perform an auditory discrimination task similar to the one adopted in the aforementioned rat experiments. High-frequency (HF, 35 Hz) light stimulations of one side of the AC1 increased the correct water retrieval rate in the contralateral hole; M40 abolished this improvement.

Our first hypothesis was confirmed: galanin released from the mPFC facilitates auditory neuronal response. The short duration of the enhancement informed our second hypothesis: galanin is involved in short-term memory (STM).

To test this hypothesis, we assessed performance differences between wild-type (WT) and galanin knockout (GalKO) mice in two STM-related experiments: the novelty-detection experiment and the passive-avoidance task. The results suggested that GalKO mice exhibited decreased STM.

The results of the present study provide convincing evidence for the direct enhancement of auditory neuronal activities evoked by galanin-positive neurons in the mPFC and suggest that galanin-containing neurons are involved in modulating STM.

    Research areas

  • galanin, primary auditory cortex, medial prefrontal cortex, short-term memory