Functions And Circuits Of Htr2c Cells In Ventral Hippocampus

Background: The hippocampal formation is an important component of the cerebral limbic system located inside the basal part of medial temporal lobe.The hippocampal formation is essential for learning and memory of humans and other vertebrates.There are several regions in the hippocampal formation.Of the essence,CA1 forms the major output of hippocampal formation for it plays an important role in almost every phase of both spatial and contextual memory.Along with a dorsal-to-ventral axis,CA1 can be divided into two parts that have distinct functions.The dorsal CA1 is critical for learning and memory,yet the basic general function of the ventral CA1 remains elusive.In reference to gene expression patterns,neurons of ventral CA1 can be further divided into three subgroups(Wfs1,Trpc4,Htr2c).Among these three subgroups,neurons expressed Htr2 c are yet to be studied.Objects: To explore the functions and circuits of Htr2 c cells in v CA1Methods : We generated Htr2c-i Cre mice on C57BL/6 background with CRISPR/Cas9 system and 3-months Htr2c-i Cre mice were used for this study.Bilaterally injected Cre recombinase dependent r AAVs into v CA1 to labeled Htr2 c cells,and then validate the properties and location of Htr2 c cells with immunostaining.After inhibited/excited Htr2 c cells,mice were measured the ability of learning and memory,attention and motility.To find specific synaptic targets of Htr2 c cells,we used genetically-modified monosynaptic tracing virus.Used whole-cell patch clamp with optogenetics to verify the neural circuit we found.At last,we studied the function of the neural circuit with behavior test.Result: The neurons,Htr2c-positive,we labeled in v CA1 were excitatory neurons,located in the deep pyramidal cell layer closer to stratum oriens.Inhibition the activity of Htr2 c cells lead to a loss of attention with 5-choice serial reaction time task(5-CSRTT),and activate these neurons with improvement of attention.We found Htr2 c cells were activated during allocation of attention with calcium imaging in vivo.Recordings of action potential firings of Htr2 c cells in freely moving mice during attention showed the similar result.We uncovered that Htr2 c cells directly innervate EW cells with multiple genetically-modified virus tracing and recording strategies.With photoactivation the terminals in EW from Htr2 c cells during attention allocated phase of 5-CSRTT,we found this neural circuit(Htr2c-EW)can also regulate attention.Conclusions: 1,Htr2 c cells form a novel subgroup of excitatory neurons in the CA1 region of the ventral hippocampus.2,Htr2 c cells play an important role during allocation of attention.3,Htr2 c cells innervate EW cells of midbrain directly,and this monosynaptic circuit regulate attention.