**4.1 The Papez circuit**

In the 1930s, Papez et al. discovered that there was a major circuit in the limbic system, called the Papez circuit, involving hippocampus→fornix→papillary body→papillary thalamic tract→prethalamic nucleus→cingulate gyrus→ hippocampus [31, 32] (**Figure 1**). The hippocampus is the central part of this circuit. This circuit acts as the neural basis for emotional expression. It has been shown that axons transmitting emotional impulses originate from the hippocampus and are projected to the thalamus through the papillary body, where physiological emotional effects such as changes in heartbeat, respiration, and body temperature are produced, and nerve fibers are projected to the cingulate gyrus and the frontal lobe of the cerebral cortex after cell replacement to produce a clear emotional experience. Finally, the signal returns to the hippocampus through the projection of the cortex, and then emotional memory will be generated. Later studies have shown that the Papez circuit is also an important brain structure closely related to learning and memory [33, 34]. Therefore, if this circuit is damaged, it will lead to the amnestic syndrome, and different lesions will produce different forms of memory impairment.

### **4.2 The trisynaptic circuit**

The trisynaptic circuit transmits signals between the entorhinal area and the hippocampus structure (**Figure 2**). This circuit first starts in the cortex of the

**Figure 1.** *The Papez circuit.*

**Figure 2.** *The trisynaptic circuit.*

entorhinal area, where neuronal axons form a perforating circuit and end in the DG granular cell dendrites [35]. The axons of the DG granular cells then form mossy fibers projecting to the hippocampal CA3 area, where they form a second synaptic connection with the dendrites of pyramidal cells. The third synaptic connection occurs between the axons of pyramidal cells in the CA3 area and dendrites of pyramidal cells in the CA1 area, and then the CA1 pyramidal cells transmit the axons to the entorhinal area. The trisynaptic circuit is, therefore, closely related to and forms an important foundation for learning and memory.

### **4.3 The entorhinal cortex (EC)**

The EC is generally perceived as a major input and output structure of hippocampal formation and contributes to cognitive processes and memory formation [36]. The EC is subdivided into two components, the lateral EC (LEC) and medial EC (MEC), according to the differential distribution of EC projections to the DG [37]. In 1893, Santiago Ramon y Cajal [38] described two classical pathways from the EC to the hippocampus (**Figure 3**). One is the long-range pathway: EC layer 2 → DG → CA3 → CA1 area; the other is the short-range or direct pathway: EC layer 3 → CA1 area. However, it is unclear how the hippocampal neurons form specific connection pathways to transmit different information, and how they participate in hippocampal learning functions. Recently, a study [4] found a direct lateral EC-dorsal CA1 (dCA1) circuit that was critically involved in olfactory associative learning. Studies have shown that excitatory pyramidal cells in the hippocampal CA1 region have highly variable molecular, morphological, and electrophysiological

**Figure 3.** *Pathways from the entorhinal cortex to the hippocampus.*

### *Neural Circuits and Some New Factors Involved in Hippocampal Memory DOI: http://dx.doi.org/10.5772/intechopen.101309*

characteristics along the dorso-ventral [39, 40], proximal-distal [40–42], and radial (superficial-deep) axes [39, 40, 43–47]. Subdivisions of deep and superficial pyramidal cells in the CA1 have been recognized for many years, especially along the radial axis. Deep and superficial pyramidal cells are generated at different times and express different genes [39, 40, 43, 48]. *In vivo* recording studies have reported different spiking patterns between these two sublayers; deep cells are more likely to burst and exhibit more spatially tuned firing than superficial cells, and they spike differentially in the hippocampal theta rhythm and during sharp-wave ripple activities [46]. Further study revealed that inhibition of the excitatory synaptic transmission from the LEC to CA1 complex pyramidal cells, or the discharge activity of the CA1 complex pyramidal cells using optogenetic methods, significantly delayed the olfactory association during mice learning [49]. The optogenetic method mentioned above is injecting NpHR or Arch into some mice's hemispheres and then using yellow illumination to identify the mice that include NpHR or Arch. Then researchers can make a comparison between special mice and normal mice. The study also implanted optetrodes into mices' dCA1 to record the olfactory-related firing activities of neurons in the CA1 region of the hippocampus, it was found that the firing of complex pyramidal cells established different preferences for odor cues during learning [49]. These experimental findings revealed that there was a specific neural pathway involved in brain-related learning in the classic circuit from the EC to hippocampus involving cells, synaptic connections, learning behaviors, and neural discharges.
