Hippocampus connections

So if ACh is involved in memory function, what does it do Any attempt to answer that question has to follow some consideration of how memory is thought to be processed. Many neuroscientists believe that memory is achieved by changes in the strength of synaptic connections (activation) between neurons and that increases in such synaptic activity somehow reinforce the pattern of neuronal activity during the memorising of an event so that it can be more easily restored later. One form of such plasticity is longterm potentiation (LTP), which has been mostly studied in the hippocampus where, as in other areas associated with memory, there is the appropriate complex synaptic morphology. 

CA3 pyramidal neurons receive the mossy fiber input from the granule neurons of the dentate gyrus. This connection is part of the 3-cell circuit of the hippocampus that is believed to be involved in learning and memory. 

Another problem in validating targets for behavioral disorders related to neurotransmitter abnormalities is the interplay between several neurotransmitter systems in specific brain regions. For example, in the hippocampus, limbic, and nigral-striatal areas, functions connected by serotonin, norepinephrine, and dopamine are interconnected so that blocking selected receptor subtypes or changing synaptic levels of certain neurotransmitters may... 

The hippocampus has innumerable afferent and efferent connections to other brain structures both within the limbic system and beyond. There are receptors for many different chemical signals ranging from the "classical neurotransmitters such as acetylcholine to steroid hormones and neurotrophic factors. Some of these receptors are located in the synapses that form the intrinsic hippocampal circuits and others are the targets of specific projection pathways from other brain areas. A comprehensive review of all neurotransmitter interactions relevant to function is not within the scope of this chapter. There are detailed reviews of modulation of neurochemical systems on place learning in the watermaze (McNamara and Skelton, 1993) or other limbic-system dependent tasks (Izquierdo and Medina, 1995) in animals. The effects of key neurochemical, other than NMDA channel-mediated, and environmental influences are discussed below. 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

The adult hippocampus also contains progenitors/ stem cells that are capable of differentiating into new hippocampal granule neurons. Hippocampal progenitor cells will give rise to new neurons in adult rodent, primate, and human brains (Eriksson et ah, 1998). The new hippocampal granule cells extend axons that are appropriately connected to the pyramidal cells in the CAS region. 

In old rats (26 months old), oral administration of EGb (10 mg/kg and 30 mg/kg, for 7 days) produces elevations of 5-HT in the frontal cortex, hippocampus, striatum and hypothalamus, and of dopamine levels in the hippocampus and hypothalamus compared with controls. On the other hand, EGb decreases the 5-HT level in the pons, and those of norepinephrine in the hippocampus and hypothalamus [157]. In this connection, Racagni et al. [158] showed that the O-methylated amine metabolite of norepinephrine, normetanephrine, was markedly elevated (+500%) in the cerebral cortex by chronic oral administration of EGb (100 mg/kg, for 14 days), suggesting an increase of norepinephrine turnover. In addition, treatment with EGb (50 or 100 mg/kg/day, for 20 days) diminished the increased plasma levels of epinephrine, norepinephrine, and corticosterone induced by acute auditory stress in young and old rats [113]. 

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