M4 Muscarinic Receptors Regulate Activity Of Place Cells In The Hippocampal CA1 Region

CA3 pyramidal cells project directly to the CA1 pyramidal cells via the Schaffer Collaterals(SC)which are important part of hippocampal tri-synaptic circuits.Previous researches have showed that M4 Muscarinic receptors are distributed in presynaptic membranes of Schaffer collaterals,and activating M4 receptors can regulate the neuronal projection of Schaffer collaterals.The concentration of acetylcholine can have significant difference in different behavioral states.When the animal is awake or in rapid eye movement sleep state,the concentration of acetylcholine is high,and the Schaffer Collaterals can be inhibited.On the contrary,when the animal is in slow wave sleep state,low concentration of acetylcholine enables CA3 to send messages to CA1.Based on these,we used in vivo recording techniques to study what would happen on pyramidal cells in CA1 while injecting tropicamide into the CA1 region when the mice are awake,to investigate the modulation of the acetylcholine to Schaffer Collaterals.A total of 111 neurons were recorded from eight mice.Among these,106 neurons are supposed to be pyramidal cells while the remaining 5 neurons are interneurons.45 pyramidal cells belong to place cells,which have respective place fields in “U” track.We analyzed the firings recorded from pyramidal cells and place cells,finding that the average frequency of both pyramidal cells and place cells have no significant difference after injecting tropicamide in CA1.However,further study indicated that 90% of place cells' place fields appeared,disappeared or shifted on the condition of tropicamide,while only 23.53% place fields changed in the control group.As for the place cells which have no significant changes in their place fields,we conducted further analysis at their firing frequency.The experimental results showed that place cells with tropicamide have a higher change ratio in peak frequency and average frequency in its' place field.Moreover,place information carried by place cells increased after injecting tropicamide.In summary the results indicate that injecting tropicamide into the CA1 region when the mice are awake can block the M4 receptors in the presynaptic of the Schaffer Collaterals,and change the firings' characteristics of the place cells,and affects spatial encoding of CA1 place cells in their place field.