Behavioral perseveration and impairment of long-term memory in rats after intrahippocampal injection of kainic acid in subconvulsive dose.
Processing of multimodal sensory information by the morphological subdivisions of the hippocampus and its input and output structures was investigated in unanesthetized rabbits by extracellular recording of neuronal activity. Analysis shows principal differences between CA3 neurons with uniform multimodal, mainly inhibitory, rapidly habituating sensory responses, and CA1-subicular neurons, substantial parts of which have phasic reactions and patterned on-responses, depending on the characteristics of the stimuli. These differences result from the organization of the afferent inputs to CA1 and CA3. Analysis of neuronal responses in sources of hippocampal inputs, their electrical stimulation, and chronic disconnection show the greater functional significance of the brain-stem reticular input for tonic responses characteristic of CA3. This input signal before entering the hippocampus is additionally preprocessed at the MS-DB relay, where it becomes more uniform and frequency-modulated in the range of theta-rhythm. It is shown that the new sensory stimuli produce inhibitory reset, after which synchronized theta-modulation is triggered. Other stimuli, appearing at the background of the ongoing theta, do not evoke any responses of the hippocampal neurons. Thus, theta-modulation can be regarded as a mechanism of attention, which prolongs response to a selected stimulus and simultaneously protects its processing against interference. The cortical input of the hippocampus introduces highly differentiated information analyzed at the highest levels of the neocortex through the intermediary of the entorhinal cortex and presubiculum. However, only CA1-subiculum receives this information directly; before its entrance into CA3, it is additionally preprocessed at the FD relay, where the secondary simplification of signals occurs. As a result, CA3 receives by its two inputs (MS-DB and FD) messages just about the presence and level of input signals in each of them, and performs relatively simple functions of determination of match/mismatch of their weights. For this comparator system, the presence of signal only in the reticulo-septal input is equivalent to quality of novelty. The cortical signal appears with some delay, after its analysis in the neocortex and shaping in the prehippocampal structures; besides, it is gradually increased due to LTP-like incremental changes in PP and mossy fiber synapses. The CA3 neurons with potentiated synapses of cortical input do not respond to sensory stimuli; that is, the increased efficacy of the cortical signals can be regarded as "familiarity" of a signal, terminating the reactive state of the CA3 neurons. The integrity of both inputs is necessary for gradual habituation of sensory responses in the hippocampus. The output signals of CA3 following in the precommissural fornix to the output relay-LS nucleus and to the brain-stem structures have strong regulatory influence on the level of brain activity (arousal), which is an important condition for processing and registration of information. The primary targets of this output signal are raphe nuclei, which suppress activity of the ascending excitatory RF. In the background state, activity of the CA3 neurons through the intermediary of raphe keeps RF under tonic inhibitory control. Inhibition of the majority of CA3 pyramidal neurons during a novel stimulus action decreases the volume of its output signal to raphe and releases RF from tonic inhibition (increase in level of activity of the forebrain, arousal). When the responses of CA3 neurons habituate, the initial high background activity is reinstated, as well as tonic suppression of RF. Analysis of the second output of CA3 (by Schaffer's collaterals to CA1) shows that activity in this pathway can block access of cortical signals from PP to CA1 neurons by action upon the local system of inhibitory neurons, or by shunting the propagation of signals in apical dendrites. Thus, CA3 can act as a filter controlling the information transmission by CA1; such transmission at any given moment is allowed only in those CA1 neurons which receive SC from CA3 neurons, responding to the sensory stimulus by suppression of their activity. Disconnection of the CA3 output fibers results in disappearance of habituation in all its target structures (raphe, RF, CA1). The output signal of CA1-subiculum follows by postcommissural fornix to the chain of structures of the main limbic circuit: mammillary bodies (medial nucleus), anterior thalamic nuclei (mainly antero-ventral nucleus), and cingulate limbic cortex (mainly posterior area). In each of these links, the signal is additionally processed. Habituation is nearly absent in these structures; instead, st