Functional Systems and Brain Functional Units Beyond Luria, With Luria: Anatomical Aspects

This paper describes the anatomical aspects of a functional brain model that develops A. R. Luria’s ideas. Five functional brain units are described on the basis of ontogenetic, anatomical, histological, functional, and clinical studies: preferential or primordial (unit I), limbic (unit II), cortical (unit III), basal ganglia (unit IV), and cerebellar (unit V). This review allows two large integrated and interrelated functional complexes to be distinguished: a primordial-limbic complex (units I and II) and a supralimbic one (units, III, IV and V). There is consensus that there exists a clear interplay among the cortex, the basal ganglia, and the cerebellum. Three main simplified parallel cortico-basal ganglia systems have been recognized: limbic, associative, and sensorimotor. Certain structures (e. g. neuromodulatory systems, hypothalamus, and paralimbic cortex) form functional links among units. Future studies are required to develop and improve the proposed model.

State-dependent cortical unit activity reflects dynamic brain state transitions in anesthesia

ABSTRACTHow anesthesia affects cortical neuronal spiking and information transfer could help understand the neuronal basis of conscious state. Recent investigations suggest that global state of the anesthetized brain is not stationary but changes spontaneously at a fixed level of anesthetic concentration. How cortical unit activity changes with dynamically transitioning brain states under anesthesia is unclear. We hypothesized that distinct cortical states are characterized by distinct neuronal spike patterns. Extracellular unit activity was measured with sixty-four-channel silicon microelectrode arrays in cortical layers 5/6 of primary visual cortex of chronically instrumented, freely moving male rats (N = 7) during stepwise reduction of the anesthetic desflurane (6, 4, 2, and 0%). Unsupervised machine learning applied to multi-unit spike patterns revealed five distinct brain states of which four occurred at various anesthetic concentrations and shifted spontaneously. In deeper anesthesia states, the number of active units and overall spike rate decreased while the remaining active units showed increased bursting (excitatory neurons), spike timing variability, unit-to-population correlation and unit-to-unit transfer entropy, especially among putative excitatory units, despite the overall decrease in transfer entropy. A novel desynchronized brain state with increased spike timing variability, entropy and electromyographic activity that occurred mostly in deep anesthesia was discovered. These results provide evidence for distinct unit activity patterns associated with spontaneous changes in local cortical brain states at stationary anesthetic conditions. The appearance of a paradoxical, desynchronized brain state in deep anesthesia contends the prevailing view of monotonic dose-dependent anesthetic effects on the brain.SIGNIFICANCE STATEMENTRecent studies suggest that spontaneous changes in brain state occur under anesthesia. However, the spiking behavior of cortical neurons associated with such state changes has not been investigated. We found that local brain states defined by multi-unit activity had non-unitary relationship with the current anesthetic level. A paradoxical brain state displaying asynchronous firing pattern and high electromyographic activity was found unexpectedly at high-dose anesthesia. In contrast, the synchronous fragmentation of neuronal spiking appeared to be a robust signature of the state of anesthesia. The findings challenge the assumption of monotonic, anesthetic dose-dependent behavior of cortical neuron populations. They enhance the interpretation of neuroscientific data obtained under anesthesia and understanding of the neuronal basis of anesthetic-induced state of unconsciousness.

Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775–1100 μm from the pial surface, discharged in a burst–pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5–15 min of the injection. The basic pattern of burst–pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.Key words: neocortex, serotonin antagonists, unit activity, noxious stimulation, desynchronization.