[The mechanisms of interdependent influence of prefrontal cortex, hippocampus and amygdala on the basal ganglia functioning and selection of behaviour].

The hypothetical mechanism of functioning of neural networks that include limbic structures, neocortex and basal ganglia is proposed. A hypothesis is based on known data that the hippocampus, amygdala and prefrontal cortex interreact with each other, that their efferents converge on spiny cells of nucleus accumbens, that these inputs are topically organised and could be modified. Since GABAergic spiny cells of nucleus accumbens innervate neurons in the output basal ganglia nuclei which inhibit excitatory transmission through the thalamic nuclei into limbic structures and neocortex, the degree of activation of neurones in mentioned structures and, hence, a behaviour selection essentially depends on the character of responses of spiny cells. A summation of excitation of spiny cells and amplification of their responses during simultaneous firing of neurons of a limbic structure and neocortex, ultimately will lead to rising in neocortical activity and increase of its influence on a behaviour selection. If two structures are excited with temporary shift, activation of neurons of that structure which has firstly been strongly excited can be additionally increased due to a disinhibition of thalamic nuclei through the basal ganglia, whereas activity of neurons in other structure can be depressed if responses of spiny cells evoked by excitation arriving from this structure are decreased. Such suppression can be a consequence of heterosynaptic depression which is based on potentiation of efficacy of excitatory inputs from the different structures converging on inhibitory interneurons in the nucleus accumbens and basolateral amygdala. As a result, the behaviour choice will be determined by that structure which has been involved in activity firstly. A damage of different inputs into the nucleus accumbens from limbic structures must result in various behaviour disorders owing to the topical organisation of these inputs.

[Investigation of features of EEG changes at psychomotor disturbanses associated with microsleep].

We tested our earlier suggested hypothesis that one of mechanisms for failures of performance of behavioural tasks during microsleep is a spontaneous generation of ponto-geniculo-occipital (PGO) waves that suppress transmission of visual information from the retina via lateral geniculate nucleus to primary visual cortical areas and the striatum, and therefore significantly impair visual perception and attention. Experiments were done during the nighttime. Monotonic testing during performance of the two-alternative psychomotor test invoked participants into a state defined as a microsleep with open eyes. For each participant we made a comparative analysis of intensity of EEG spectrum during state of microsleep with open eyes when failure in test performance occurred and during accurate performance in waking state. Following trends in changes of EEG spectrum were found: increase in intensity of low alpha-range, and decrease in intensity of high alpha- and beta-ranges. Changes in theta-, low beta- and gamma-ranges were differently directed. Taking into account the known from the literature data these changes specify decrease in activation of primary visual cortical areas. Revealed data could support our hypothesis concerning mechanism of visual-motor disturbances during microsleep with open eyes.

[Possible mechanisms for orexin effects on the functioning of the hippocampus and spatial learning (analytical review)].

We analyzed possible mechanisms for the influence of the "wakening hormone" orexin on spatial learning acting via changes in the functioning of the hippocampus and connected structures. The literature data point out that, firstly, orexin can directly potentiate excitation of neurons in different hippocampal areas by acting on Gq/11-protein-coupled postsynaptic OX1 and OX2 receptors. Due to facilitation of induction of the long-term potentiation of excitatory transmission at each stage of trisynaptic pathway through the hippocampus, orexin can promote transduction of information through this structure and formation of neural representations of object-place associations. Secondly, orexin can increase the release of acetylcholine, GABA and glutamate in the hippocampus by enhancing activity of neurons in the medial septum that have OX1 and OX2 receptors. This could lead to changes in intensity and frequency of the hippocampal theta rhythm. Thirdly, orexin can influence the functioning of reinforcing networks that include neurons of the hippocampus, prefrontal cortex, amygdala, ventral striatum, and ventral tegmental area by direct modulation of their activity through OX receptors. By enhancing the activity of dopaminergic neurons and increasing dopamine release, orexin can improve the functioning of reinforcing networks and facilitate spatial learning.

[Possible mechanisms of learning, memory and attention impairment in consequence of sleep deprivation].

We proposed that impairment of learning, memory, and attention evoked by sleep deprivation could be a consequence of following changes in neuromodulator concentrations and intracellular processes that influence synaptic plasticity and functioning of the hippocampal formation and cortico--basal ganglia--thalamocortical loops. Firstly, a decrease in Ca2+ concentration and NMDA-receptor expression prevents induction of LTP of efficacy of synaptic transmissions in the neocortex and hippocampus. Secondly, a decrease in orexin concentration also worsens conditions for LTP induction and suppresses transmission of excitation in trisynaptic pathway through the hippocampus, thus worsening a creation of neural representations of "object-place" associations. Thirdly, a decrease in concentration of dopamine, and increase in level of adenosine and number of A1 receptors in the striatum worsen the functioning ofcortico-basal ganglia-thalamocortical loops. These lead to decrease in voluntary and involuntary attention, worsens processing of sensory information, and motor reactions. Excitation of neurons in reinforcement loops is also decreased thus suppressing the motivational significance of stimuli.

Co-oximetry in clinically healthy dogs and effects of time of post sampling on measurements.

OBJECTIVES: Co-oximetry is a complex and valuable laboratory method that measures haemoglobin species and oxygenation status by multi-wavelength spectrophotometry. The purpose of this study was to establish reference intervals for clinically healthy dogs and to determine the effect of time of analyses and sex of animals on the accuracy of results. METHODS: Blood was collected from 27 healthy adult dogs of various breeds and sex. Co-oximetry was performed on a CCX co-oximeter that measures eight haemoglobin and oxygen transport related parameters: carboxyhaemoglobin (COHb), deoxyhaemoglobin (HHb), oxyhaemoglobin (O(2)Hb), methaemoglobin (MetHb), total haemoglobin (tHb), oxygen saturation (SO(2)%), oxygen content (O(2)Ct) and oxygen capacity (O(2)Cap). RESULTS: Results obtained after 2 and 4 hours were not significantly different from those obtained immediately after sampling. But after 48 hours, the results for total haemoglobin, oxygen saturation, oxyhaemoglobin, oxygen content and oxygen capacity were significantly lower, and carboxyhaemoglobin and deoxyhaemoglobin values were significantly higher than determination immediately after sampling. Gender had no significant impact on co-oximetry values. CLINICAL SIGNIFICANCE: Co-oximetry offers several advantages compared with other methods, including ease of use, increased accuracy and greater differentiation among haemoglobin species.

[Generation of Ponto-Geniculo-Occipital (PGO) waves as a possible reason of disturbances in visual perception in microsleep].

A hypothesis is put forward that one of the reasons for disturbances in visual perception during microsleep could be a spontaneous generation of Ponto-Geniculo-Occipital (PGO) waves. If the PGO waves are generated in microsleep, they could propagate into different thalamic nuclei conveying visual infomation. Consequently, a propagation of visual infonnation from the retina (if the eyes are opened) to visual neocortical areas and to input basal ganglia nucleus, striatum could be impaired. According to previously proposed mechanism of visual processing, which includes visual attention, in absence of striatum activation by a visual stimulus, a disinhibition through the basal ganglia of superior colliculus that transfer visual information to dopaminergic structures becomes impossible. Due to absence of dopamine release in response to visual stimulus, the attention to this stimulus cannot start, and therefore its processing worsens in all visual cortical areas. The suggested hypothesis could be verified in experiments with artificially evoked microsleep using non-invasive methods for searching for the correlates of the PGO activity presence in the brain.

[A possible mechanism of participation of neuronal loops cortex - basal ganglia - thalamus - cortex in time perception].

A mechanism of time perception is suggested. It is based on a postulate that time when stimulus arrives (parameter "when") is such property of stimulus as its physical properties (parameters "what"), and association "what - when" is perceived in those area of neocortex in which property "what" is processed after its repeated excitation. The time of repeated excitation which determines clock rate of "intrinsic clock", depends on dopamine influence at functioning of the cortico - basal ganglia - thalamocortical loop that promotes contrasted amplification of activity of cortical neurones, firstly activated by stimulus. Accumulation of time counts is performed in the neocortex and coded by the number of neuronal discharges. Duration of current interval is proportional to the number and duration of cycles of repeated neocortical excitation. Time counting can be started involuntary by stimulus, or voluntary due to activation of prefrontal cortex. The mechanism of time perception is similar for stimuli of different modalities owing to resemblance of functioning of topically organised cortico - basal ganglia - thalamocortical loops, it follows from our model that the more (less) concentration of dopamine in the striatumm the higher (low) clock rate, so the real interval will be estimated more (less) precisely and perceived as longer (short). These consequences of the model are in accordance with known experimental data.

[Benefits of hierarchical generalization and storage of the representations of "object-place" associations in the hippocampal subfields (a hypothesis)].

We analyzed the results of experimental research of features of processing sensory information in the hippocampus and neocortex available in literature and results of modelling the perception of information in the neocortex. It is noted that "place" fields of neurons become wider, and overlapping of receptive fields increases during upward moving in trisynaptic hippocampal pathway. These effects specify the generalization of the information processed. The results of our analysis allow us to put forward a hypothesis that a hierarchical complication of"object - place" associations occurs during upward propagation of signals through all hippocampal subfields. Complexity of neural representations of "object - place" associations that are formed and permanently stored in the hippocampal areas increases in process of propagation of signals from the entorhinal cortex to the hierarchically higher dentate gyrus, area CA3 and area CA1. Therefore, with the aim to extract information about "object - place" associations with certain details it is necessary to access that hippocampal area in which associations were processed and stored with the required degree of elaboration. By analogy with the neocortex, it is proposed that such processing of information in the hippocampus makes it possible to avoid the combinatorial explosion and provides storing (memory) the associations accumulated during the life. The proposed mechanism can serve as an addition to the known multiple trace theory, which states that the hippocampus is an integrating part of memory trace and is always involved in recall of long-delayed episodes.

[Intoxication by alcohol and substitutes: prehospital diagnosis and emergency medical care].

The paper considers the pathogenesis, clinical picture, and diagnosis of acute intoxications with alcohol and substitutes, and its prehospital medical care. It details an emergency team's tactics in patients with the above conditions.

Paradoxical sleep as a tool for understanding the hippocampal mechanisms of contextual memory.

Existing data on the involvement of the hippocampus in contextual memory and the fact that contextual memory is impaired in dreams occurring during paradoxical sleep allowed us to suggest that one of the causes of this impairment consists of changes in the efficiency of synaptic transmission in the hippocampus due to increases (as compared with waking) in the concentrations of acetylcholine, dopamine, and cortisol, as well as the absence of serotonin and noradrenaline. Our previous analysis showed that in paradoxical sleep, long-term depression can be induced all components of the polysynaptic pathway through the hippocampal formation, while potentiation can occur at the inputs from the entorhinal cortex to hippocampal fields CA1 and CA3 and in the associative connections in field CA3. It is hypothesized that the correct functioning of episodic memory requires efficient transmission of signals in each component of the polysynaptic pathway through the hippocampus, allowing a neuronal representation of the context to be created within it. In the state of waking, reproduction of the context of an episode simultaneously activates the neuronal representation of the context remembered in the hippocampus and neuronal representations of the details of the episode remembered in those areas of the cortex in which they were processed. It follows from the proposed mechanism that any neurotransmitter or neuropeptide able to promote longterm potentiation in all components of the polysynaptic pathway through the hippocampus can improve episodic memory. As the consequences of the mechanism are consistent with experimental data, it can be used to seek agents improving episodic memory.

Characteristics of the functioning of the hippocampal formation in waking and paradoxical sleep.

Analysis of published data identifying different neurotransmitter concentrations in the brain in paradoxical sleep and waking and data on the influences of neurotransmitters on the efficiency of the synaptic inputs to hippocampal neurons led to the conclusion that increases in the acetylcholine, cortisol, and dopamine concentrations during paradoxical sleep, with simultaneous reductions in serotonin and noradrenaline levels, may lead synergistically to a significant depression of transmission efficiency in polysynaptic pathways running through the hippocampus (i.e., the perforant path to neurons of the dentate gyrus, the pathway from the dentate gyrus to field CA3, from field CA3 to field CA1, and from field CA1 to the subiculum) but also to potentiation of the efficiency of the perforant path to pyramidal neurons of fields CA1 and CA3 and increases in the efficiency of associative connections between neurons in field CA3. This pattern of changes in the functioning of the hippocampal formation circuit may underlie differences in remembering and extracting information from memory in paradoxical sleep as compared with waking.

[Involvement of trisynaptic hippocampal pathway in generation of neural representations of object-place associations (analytical review)].

A review. Possible mechanisms for generation of neural representations of object-place associations (NROPA) are analyzed in different parts of a neural network which include the hippocampus and parahippocampal complex. Streams of spatial and non-spatial information arrive to the hippocampus from the parahippocampal complex consisting of perirhinal, postrhinal and entorhinal cortical areas. We assume that, due to the absence of connections between lateral and medial areas of the entorhinal cortex, object-place associations are mostly formed in the hippocampus, but can also be generated in the perirhinal cortex due to existence of input from the postrhinal cortex. As both information streams converge on neurons of the dentate fascia and field CA3, a trisynaptic pathway through the hippocampus can play the basic role in the NROPA generation. Since the spatial information arrives in the neocortex and, therefore, reaches the parahippocampal complex and hippocampus approximately by 20 ms earlier than the "non-spatial" stream, only spatial information is processed firstly in the dentate fascia and field CA3. Generation of NROPA in the dentate fascia starts later, due to returning excitation from field CA3c. In the dentate fascia, signals from the NROPA are transferred into field CA3, where the activated neuronal pattern is superimposed by information arriving from the entorhinal cortex. As a result, more complex NROPA are formed in field CA3 and send signals to field CA1. In the dorsal (ventral) part of the field CA1, the activated neuronal pattern is superimposed by non-spatial (spatial) information arriving from the lateral (medial) part of the entorhinal cortex. As a result, a higher-order NROPA are generated. In the parahippocampal cortex, the generation ofNROPA can be a consequence of the activity transferred from the dorsal part of the hippocampal CA1 field.

[Paradoxical sleep as a tool for understanding hippocampal mechanisms of contextual memory].

Existing data on hippocampal involvement in contextual memory and the fact that contextual memory is deranged during REM sleep dreams allowed us to assume that one of the reasons for this derangement could be a change in the efficacy of synaptic transmission in the hippocampus because of a rise (as compared to wakefulness) of acetylcholine, cortisol, and dopamine concentrations and lack of serotonin and norepinephrine. The earlier performed analysis showed that, during REM sleep, the LTD could be induced at all steps of the polysynaptic pathway through the hippocampal formation, whereas the LTP could be induced in the entorhinal inputs to hippocampal areas CA1 and CA3 and in associative connections within the CA3 field. We suggested that the effective signal transmission in each units of the polysynaptic pathway through the hippocampus is necessary for correct functioning of episodic memory and generation of neuronal representation of the context. During retrieval in the state of wakefulness, the representation of episodic context stored in the hippocampus could be activated together with the neuronal representations of episodic details stored in those neocortical areas wherein they were processed. It follows from the proposed mechanism that any neuromodulator or neuropeptide which promotes LTP in the polysynaptic hippocampal pathway can improve episodic memory. Since the consequences of the proposed mechanism agree with the known experimental data, this phenomenon can be used for the development of drugs improving episodic memory.

[Characteristics of the hippocampal formation functioning during wakefulness and paradoxical sleep].

In view of the available published data concerning various concentration of neuromodulators in the brain during paradoxical sleep and wakefulness and the evidence for the influences of neuromodulators on efficiency of synaptic inputs to hippocampal neurons it is concluded that during paradoxical sleep, increase in concentrations of acetylcholine, cortisol, and dopamine and simultaneous decrease in serotonin and noradrenaline levels could synergistically lead to essential depression of efficacy of synaptic transmission in the polysynaptic pathway through the hippocampus (i.e. in the perforant path to dentate gyrus, from the dentate gyrus to CA3 area, from CA3 to CA1 area and from CA1 to the subiculum) but potentiation of the efficacy of the perforant input to pyramids of CA1 and CA3 areas and increase in efficacy of associative connections between CA3 neurones. The specified changes in functioning of the hippocampal loop can underlie differences in storing and extraction of information from memory during paradoxical sleep as compared to wakefulness.

Poisoning of a dog with the explosive pentaerythrityl tetranitrate.

A three-year-old male Labrador retriever was presented at the Clinic of Internal Medicine, University of Zagreb, Croatia. The owner reported that the dog was ataxic, and this was evident by its markedly unsteady, swaying gait. The dog also had difficulty rising and fell several times while trying to stand. It had come into contact with the explosive, pentaerythrityl tetranitrate, while training to detect explosives. The following clinical symptoms were observed: bradycardia, depression, mild disorientation and a broad-based stance. The dog had conscious proprioceptive deficits in the hindlimbs, but cranial nerve function was normal except for miosis. Ion scan analysis of the dog's serum after evaporation of the current phase by mass spectroscopy revealed the presence of fragments that are characteristic of pentaerythrityl tetranitrate. The aim of the present case report was to identify pentaerythrityl tetranitrate poisoning and describe the clinical signs of pentaerythrityl tetranitrate poisoning in dogs. To the authors' knowledge, there are no published scientific articles on pentaerythrityl tetranitrate poisoning in dogs.

The role of dopamine-dependent negative feedback in the hippocampus-basal ganglia-thalamus-hippocampus loop in the extinction of responses.

A mechanism for the extinction of the responses of hippocampal and dopaminergic neurons to repeated sensory stimuli is proposed, based on dopamine-dependent negative feedback in the hippocampus-basal ganglia-thalamus-hippocampus loop. Activation of hippocampal neurons evoked by a new stimulus facilitates the appearance of responses in dopaminergic neurons as a result of disinhibition via striopallidal cells of the nucleus accumbens and ventral pallidum. However, increases in dopamine levels and activation of D2 receptors on striopallidal cells, facilitating depression of hippocampal inputs, prevent disinhibition of dopaminergic neurons, such that their responses start to decline. Subsequent reductions in actions on D1 receptors lead to decreases in the efficiency of excitation both of neurons in hippocampal field CA1 and strionigral cells in the nucleus accumbens. The direct pathway via the basal ganglia mediates disinhibition of the thalamic nucleus reuniens, exciting neurons in field CA1, which leads to extinction of the responses of hippocampal neurons, decreases in disinhibition of dopaminergic cells, and further extinction of their responses.

[Workplace mobbing]. / zlostavljanje na radnome mjestu.

Workplace mobbing is a hostile and unethical communication, systematically aimed from one or more individuals towards mostly one individual, who are forced into a helpless position and are held in it by constant bullying. This article describes some of the most important characteristics of mobbing: offensive behaviour, organizational and non-organizational causes of this behaviour, the victim and the consequences. Modern business environment is complex, dynamic, volatile, and requires better ability to adjust. Constant changes are a part of organizational reality, but they also produce an ideal environment for all kinds of conflicts. Conflicts are inevitable in every organization, but the task of its management is to identify them and resolve before they affect the workforce, productivity and costs. The idea is to avert psychological abuse and aberrant behaviour such as mobbing which that may cause physical and mental disorders. Mobbing is a problem of the modern society; as a violation of human rights it is relatively new and unrecognised in Croatia. Abuse is mostly psychological: it affects the victim's health and life, quality of work, productivity, profitability, and may lead to significant economic losses in the community. Mobbing can be averted by joint forces that would involve employee and management, medical and legal professionals, and even community as a whole. The more an organization pursues excellence based on trust and business ethics, the higher the probability that mobbing will be averted or stopped.

[A role of dopamine-dependent activity reorganizations in the cortico-basal ganglia-thalamocortical loops in visual attention (hypothetical mechanism)].

A mechanism of attention is proposed according to which its influence on visual processing is switched on by release of dopamine into the striatum. A dopamine release during involuntary attention is promoted by visual activation of striatonigral cells via the thalamus and subsequent disinhibition through the basal ganglia of the superior colliculus. A dopamine release during voluntary attention is promoted by activation of prefrontal cortex. The strengthening of responses of neocortical neurons to attended stimulus, and suppression of responses to other stimuli is the result of opposite modulatory action of dopamine on the efficacy of strong and weak corticostriatal inputs. This leads to changes in the output basal ganglia signals ("attentional filter") that exert disinhibitory and inhibitory influence (via the thalamus) on neocortical cells that initially were strongly and weakly activated by a stimulus, respectively. From proposed mechanism follows, that attention modulates only those components of responses of cortical neurons which latency exceeds the latency of reactions of dopaminergic cells (80-100 ms).

The contribution of synaptic plasticity in the basal ganglia to the processing of visual information.

A mechanism for the involvement of the basal ganglia in the processing of visual information, based on dopamine-dependent modulation of the efficiency of synaptic transmission in interconnected parallel associative and limbic cortex-basal ganglia-thalamus-cortex circuits, is proposed. Each circuit consists of a visual or prefrontal area of the cortex connected with the thalamic nucleus and the corresponding areas in different nuclei of the basal ganglia. The circulation of activity in these circuits is supported by the recurrent arrival of information in the thalamus and cortex. Dopamine released in response to a visual stimulus modulates the efficiencies of "strong" and "weak" corticostriatal inputs in different directions, and the subsequent reorganization of activity in the circuit leads to disinhibition (inhibition) of the activity of those cortical neurons which are "strongly" ("weakly") excited by the visual stimulus simultaneously with dopaminergic cells. The pattern in each cortical area is the neuronal reflection of the properties of the visual stimulus processed by this area. Excitation of dopaminergic cells by the visual stimulus via the superior colliculi requires parallel activation of the disinhibitory input to the superior colliculi via the thalamus and the "direct" pathway" in the basal ganglia. The prefrontal cortex, excited by the visual stimulus via the mediodorsal nucleus of the thalamus, mediates the descending influence on the activity of dopaminergic cells, simultaneously controlling dopamine release in different areas of the striatum and thus facilitating the mutual selection of neural reflections of the individual properties of the visual stimulus and their binding into an integral image.

[Role of dopamine-dependent negative feedback in the hippocampal--basal ganglia--thalamo---hippocampal loop in response decrement].

The mechanism of response decrement in hippocampal and dopaminergic neurons on repeating stimuli based on the dopamine-dependent negative feedback in the hippocampal--basal ganglia--thalamo--hippocampal loop is suggested. Activation of hippocampal neurons caused by new stimulus facilitates occurrence of reaction of dopaminergic cells due to their disinhibition through striatopallidal cells of nucleus accumbens and ventral pallidum. However, increase in dopamine level and activation accumbens and ventral pallidum. However, increase in dopamine level and activation of D2 receptors on the striatopallidal cell, while promoting depression of hippocampal inputs, prevents disinhibition of dopaminergic cells, and their reactions start their decrement. The subsequent decrease in D1 receptor activation leads to reduction of efficiency of neuron excitation in the hippocampal CA1 fields, as well as in striatonigral cells of nucleus accumbens. This leads to a decrease of disinhibition through a direct pathway via the basal ganglia of thalamic nucleus reunions which activates neurons of the CA1 field. This effect causes decrement of reactions of the hippocampal neurons, a subsequent reduction of dopaminergic cell disinhibition, and further decrement of their responses.