Somatostatin expressing GABAergic interneurons in the medial entorhinal cortex preferentially inhibit layerIII-V pyramidal cells.

GABA released from heterogeneous types of interneurons acts in a complex spatio-temporal manner on postsynaptic targets in the networks. In addition to GABA, a large fraction of GABAergic cells also express neuromodulator peptides. Somatostatin (SOM) containing interneurons, in particular, have been recognized as key players in several brain circuits, however, the action of SOM and its downstream network effects remain largely unknown. Here, we used optogenetics, electrophysiologic, anatomical and behavioral experiments to reveal that the dendrite-targeting, SOM+ GABAergic interneurons demonstrate a unique layer-specific action in the medial entorhinal cortex (MEC) both in terms of GABAergic and SOM-related properties. We show that GABAergic and somatostatinergic neurotransmission originating from SOM+ local interneurons preferentially inhibit layerIII-V pyramidal cells, known to be involved in memory formation. We propose that this dendritic GABA-SOM dual inhibitory network motif within the MEC serves to selectively modulate working-memory formation without affecting the retrieval of already learned spatial navigation tasks.

Ventromedial prefrontal cortex is involved in preference and hedonic evaluation of tastes.

The ventromedial prefrontal cortex (vmPFC) of rats has reciprocal connections with the gustatory and the hedonic impact coding structures. The main goal of the present study was to investigate the involvement of local neurons of vmPFC and their catecholaminergic innervations in taste preference and taste reactivity test. Therefore, kainate or 6-hydroxydopamine (6-OHDA) lesions were performed in the vmPFC by iontophoretic method. In the first experiment, taste preference was tested to 250 mM and 500 mM glucose solutions over water in two-bottle choice test. In the second experiment, taste reactivity was examined to 4 concentrations of glucose solutions (250 mM, 500 mM, 750 mM and 1000 mM) and 4 concentrations of quinine solutions (0.125 mM, 0.25 mM, 1.25 mM and 2.5 mM). Our results showed, that kainate microlesion of vmPFC did not modify the preference of 250 mM and 500 mM glucose solutions in two-bottle choice test. In contrast, 6-OHDA microlesion of vmPFC resulted in increased preference to the higher concentration of glucose (500 mM) solution over water. Results of taste reactivity test showed that kainate lesion resulted in more ingestive and less rejective responses to 750 mM glucose solution and elevated rejectivity to the higher concentrations (1.25 mM and 2.5 mM) of quinine solutions. 6-OHDA lesion of vmPFC increased the number of ingestive responses to highly concentrated (500 mM, 750 mM and 1000 mM) glucose solutions and decreased the number of ingestive responses to the lower concentration (0.125 mM) of quinine solution. The present data provide evidence for the important role of vmPFC neurons and catecholaminergic innervation of the vmPFC in the regulation of hedonic evaluation of tastes and in the hedonic consummatory behavior.

Iontophoretic microlesions with kainate or 6-hydroxidopamine in ventromedial prefrontal cortex result in deficit in conditioned taste avoidance to palatable tastants.

Effects of kainate or 6-hydroxidopamine (6-OHDA) lesions in the ventromedial prefrontal cortex (vmPFC) on taste-related learning and memory processes were examined. Neurotoxins were applied by iontophoretic method to minimize the extent of lesion and the side effects. Acquisition and retention of conditioned taste avoidance (CTA) was tested to different taste stimuli (0.05 M NaCl, 0.01 M saccharin, 0.01 M citrate and 0.00025 M quinine). In the first experiment, palatability index of taste solutions with these concentrations has been determined as strongly palatable (NaCl, saccharin), weakly palatable (citrate) and weakly unpalatable (quinine) taste stimuli. In two other experiments vmPFC lesions were performed before CTA (acquisition) or after CTA (retrieval). Our results showed that both kainate and 6-OHDA microlesions of vmPFC resulted in deficit of CTA acquisition (to NaCl, saccharin and citrate) and retrieval (to NaCl and saccharin). Deficits were specific to palatable tastants, particularly those that are strongly palatable, and did not occur for unpalatable stimulus. The present data provide evidence for the important role of vmPFC neurons and catecholaminergic innervation of the vmPFC in taste related learning and memory processes.

Destruction of noradrenergic terminals increases dopamine concentration and reduces dopamine metabolism in the medial prefrontal cortex.

Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. Six-hydroxy-DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in separate groups of animals. In addition, GBR 12935 or vehicle was injected into the mPFC in two other groups of animals as control experiments. NE and DA concentrations from postmortem tissue of the mPFC were measured using HPLC with electrochemical detection. In addition, extracellular NE, DA and DOPAC levels were determined using in vivo microdialysis after the 6-OHDA lesion in combination with GBR 12935 pretreatment in the mPFC. Using reverse microdialysis of alpha-2-adrenoreceptor antagonist yohimbine, we tested the remaining activity of NE innervation and the extracellular concentration of DA and DOPAC. NE and DA concentrations from postmortem tissue of the mPFC showed that 6-OHDOPA lesion reduced NE concentration to 76%, which was a non-significant alteration, however it enhanced significantly DA concentration to 186% compared to vehicle. After 6-OHDA lesion with GBR 12935 pretreatment, concentration of NE significantly decreased to 51% and DA level increased to 180%. 6-OHDA lesion without GBR 12635 pretreatment decreased NE concentration to 23% and DA concentration to 67%. In the microdialysis experiment, after 6-OHDA lesion with GBR 12935 pretreatment, extracellular NE levels were not detectable, whereas extracellular DA levels were increased and DOPAC levels were decreased compared to controls. Reverse microdialysis of yohimbine demonstrated that the residual NE innervation was able to increase NE level and DA levels, but DOPAC concentration remained low after lesion of the NE terminals. These findings suggest that the damage of NE innervation in the mPFC may alter extracellular DA level due to a reduced DA clearance.

The MAM-E17 schizophrenia rat model: Comprehensive behavioral analysis of pre-pubertal, pubertal and adult rats.

The MAM-E17 model is one of the most accepted schizophrenia rat models, which follows the neurodevelopmental theory of the disease. While symptoms of MAM-E17 rats were studied extensively, their examinations were usually restricted to adulthood and in a few cases to prepuberty. It is well known, however, that schizophrenia symptoms often start at puberty or early adulthood. Therefore the purpose of this study was to investigate the behavioral characteristics of MAM-E17 rats in various tests throughout three different age-periods, namely in prepuberty, late puberty and adulthood. In open field test, MAM-E17 rats displayed increased locomotor activity, elevated sniffing frequency and, as tendency, enhanced rearing activity. The elevated activity turned up in late puberty and remained there in adulthood, too. There was also a deficient prepulse inhibition (PPI) of startle response in late puberty and adulthood, but not before puberty. In rotarod task, MAM-treated rats performed better than control rats. The enhanced performance on rotarod was only present in late puberty and adulthood. In elevated plus maze test MAM-treated rats displayed diminished anxiety mostly in prepuberty. Histological analysis revealed reduced volume and cell disarray in the dorsal hippocampus. This is the first comprehensive study about symptoms of MAM-E17 rats manifested in behavioral tests carried out in prepuberty, late puberty and adulthood. Results display the age-dependent appearance of schizophrenia symptoms in the same rats. The present findings provide basic information to accomplish the schizophrenia related animal research, as well as can also confer further data to develop preventive treatment for human patients.

Temporal properties of colour opponent receptive fields in the cat lateral geniculate nucleus.

The primordial form of mammalian colour vision relies on opponent interactions between inputs from just two cone types, 'blue' (S-) and 'green' (ML-) cones. We recently described the spatial receptive field structure of colour opponent blue-ON cells from the lateral geniculate nucleus of cats. Functional inputs from the opponent cone types were spatially coextensive and equally weighted, supporting their high chromatic and low achromatic sensitivity. Here, we studied relative cone weights, temporal frequency tuning and visual latency of cat blue-ON cells and non-opponent achromatic cells to temporally modulated cone-isolating and achromatic stimuli. We confirmed that blue-ON cells receive equally weighted antagonistic inputs from S- and ML-cones whereas achromatic cells receive exclusive ML-cone input. The temporal frequency tuning curves of S- and ML-cone inputs to blue-ON cells were tightly correlated between 1 and 48 Hz. Optimal temporal frequencies of blue-ON cells were around 3 Hz, whereas the frequency optimum of achromatic cells was close to 10 Hz. Most blue-ON cells showed negligible response to achromatic flicker across all frequencies tested. Latency to visual stimulation was significantly greater in blue-ON than in achromatic cells. The S- and ML-cone responses of blue-ON cells had on average, similar latencies to each other. Altogether, cat blue-ON cells showed remarkable balance of opponent cone inputs. Our results also confirm similarities to primate blue-ON cells suggesting that colour vision in mammals evolved on the basis of a sluggish pathway that is optimized for chromatic sensitivity at a wide range of spatial and temporal frequencies.

Neuronal coding of auditory sensorimotor gating in medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is thought to be an essential brain region for sensorimotor gating. The exact neuronal mechanisms, however, have not been extensively investigated yet by delicate single unit recording methods Prepulse inhibition (PPI) of the startle response is a broadly used important tool to investigate the inhibitory processes of sensorimotor gating. The present study was designed to examine the neuronal mechanisms of sensorimotor gating in the mPFC in freely moving rats. In these experiments, the animals were subjected to both pulse alone and prepulse+pulse stimulations. Head acceleration and the neuronal activity of the mPFC were simultaneously recorded. To adequately measure the startle reflex, a new headstage with 3D-accelerometer was created. The duration of head acceleration was longer in pulse alone trials than in prepulse+pulse trial conditions, and the amplitude of head movements was significantly larger during the pulse alone than during the prepulse+pulse situations. Single unit activities in the mPFC were recorded by means of chronically implanted tetrodes during acoustic stimulation evoked startle response and PPI. High proportion of medial prefrontal cortical neurons responded to these stimulations by characteristic firing patterns: short duration equal and unequal excitatory, medium duration excitatory, and long duration excitatory and inhibitory responses were recorded. The present findings, first time in the literature, demonstrated the startle and PPI elicited neuronal activity changes of the mPFC, and thus, provided evidence for a key role of this limbic forebrain area in sensorimotor gating process.

[MAM-E17 schizophrenia rat model]. / A MAM-E17 szkizofrénia patkánymodell.

Schizophrenia is a serious neuropsychiatric disorder. Several brain structures, neurotransmitter systems, genetic and environmental risk factors are suspected in the background. Because of its complexity the mechanism of the disorder is not known exactly, so the treatment of patients is unsolved. In the research of schizophrenia application of the rodent models is widespread. In this study one of these models based on the effect of methylazoxymethanol- acetate (MAM) is described, which is a neurodevelopmental, validated rat model. This antimitotic agent is able to evoke a number of schizophrenic symptomes temporarily disrupting the prenatal neurogenesis. The model reproduces numerous histological and neurophysiological changes of the human disorder, moreover it also represents several behavioral and cognitive phenomena resembling those in schizophrenia. A salient advantage of the model is the demonstration of the diachronic feature of the disorder, that is, postpubertal appearance of the positive symptoms. This model provides widespread opportunities for manipulations of the symptoms, so that using it in the future investigations can lead to a better understanding of this disorder.

Responses of rat medial prefrontal cortical neurons to Pavlovian conditioned stimuli and to delivery of appetitive reward.

In the present experiments, medial prefrontal cortical (mPFC) neurons were extracellularly recorded by means of tetrode electrodes to examine their possible role in the prediction of appetitive reward. Two different cue tones (CS) and sucrose solution or water reward (US) were associated in a Pavlovian conditioning paradigm. In order to test behavioral correlate of the CS-US association, the head acceleration before the first lick of licking cluster was measured. Neuronal activity changes in the mPFC were analyzed (i) during the CS presentations; (ii) before the first lick of licking clusters; (iii) during consummation; and (iv) we also examined whether consummation was represented in neurons responding to the CSs. There was a difference between the head accelerations to the different USs during early or late occurring first approaches, but there was no such a difference during intercluster approaches. A significant proportion of neurons changed their firing rate during the CS presentation, before the first lick of licking cluster or during licking of the reward. Both, excitatory and inhibitory responses were observed. A subpopulation of neurons responding to the CSs also responded during reward consumption. Differential population activities of excitatory neurons were recorded in response to the different CSs, CS evoked approach behaviors and consumption of different rewards. Neuronal responses also discriminated among the CSs and trials with or without consummation. These results provided evidence for the involvement of mPFC neurons in the prediction, representation and organization of conditioned behavioral actions, such as approaches to rewards and consummation.

The role of catecholamine innervation in the medial prefrontal cortex on the regulation of body weight and food intake.

Effects of 6-hydroxydopamine (6-OHDA) lesions in the medial prefrontal cortex with or without protection of norepinephrine (NE) fibers were examined on basic regulatory processes of feeding. Daily body weight, food and water intake were measured. Locomotor activity, ingestion after food or water deprivation, and preference for 5% and 10% glucose solution were examined. Dopamine (DA) and NE content, as well as, tyrosine hydroxylase immunoreactivity were assessed to confirm the neurotoxic effect of treatments. 6-OHDA lesions of the medial prefrontal cortex with or without NE fiber protection resulted in body weight loss. Diminished habituation in open field tests, i.e. a persistently high motor activity, was also observed. Application of 6-OHDA with NE fiber protection led to increased food consumption following food-deprivation and to enhanced glucose preference. Enhanced intake of 10% over 5% glucose solution was also detected. 6-OHDA lesion resulted in a decrease to 20% of NE tissue concentration and only to 75% of DA concentration. In case of lesion with NE protection the NE content decreased to 69% and DA level to 51% with significant loss of tyrosine hydroxylase positive fibers in the deeper layers of the medial prefrontal cortex. DA depletion in the medial prefrontal cortex resulted in increased behavioral responsiveness to hunger and glucose, as well as, to open field environment. Pronounced lesion of NE terminals caused increased reaction to the environment in open field but not to hunger or glucose solution.

Receptive field properties of color opponent neurons in the cat lateral geniculate nucleus.

Most nonprimate mammals possess dichromatic ("red-green color blind") color vision based on short-wavelength-sensitive (S) and medium/long-wavelength-sensitive (ML) cone photoreceptor classes. However, the neural pathways carrying signals underlying the primitive "blue-yellow" axis of color vision in nonprimate mammals are largely unexplored. Here, we have characterized a population of color opponent (blue-ON) cells in recordings from the dorsal lateral geniculate nucleus of anesthetized cats. We found five points of similarity to previous descriptions of primate blue-ON cells. First, cat blue-ON cells receive ON-type excitation from S-cones, and OFF-type excitation from ML-cones. We found no blue-OFF cells. Second, the S- and ML-cone-driven receptive field regions of cat blue-ON cells are closely matched in size, consistent with specialization for detecting color contrast. Third, the receptive field center diameter of cat blue-ON cells is approximately three times larger than the center diameter of non-color opponent receptive fields at any eccentricity. Fourth, S- and ML-cones contribute weak surround inhibition to cat blue-ON cells. These data show that blue-ON receptive fields in cats are functionally very similar to blue-ON type receptive fields previously described in macaque and marmoset monkeys. Finally, cat blue-ON cells are found in the same layers as W-cells, which are thought to be homologous to the primate koniocellular system. Based on these data, we suggest that cat blue-ON cells are part of a "blue-yellow" color opponent system that is the evolutionary homolog of the blue-ON division of the koniocellular pathway in primates.

Neuronal activity in rat medial prefrontal cortex during sucrose solution intake.

The rat's prefrontal cortex plays a role in integration of feeding-related information. In this study, we investigated the neuronal activity changes of medial prefrontal cortex during licking of sucrose solution by freely moving rats. We found two different types of excitatory and two different types of inhibitory single neuron responses time locked to the beginning of the licking clusters. Changes in firing rates occurred either within 2 s before the first lick of the licking cluster or during the licking cluster. These observations suggest that neuronal responses in the medial prefrontal cortex may represent anticipation and consummation of liquid food reward.

Implementation of a galvanically isolated low-noise power supply board for multi-channel headstage preamplifiers.

Custom made multi-channel headstage preamplifiers are traditionally powered by battery. By the use of an isolated unregulated DC/DC converter integrated circuit (DCP010512B from Texas Instruments Inc., TX, USA), here we describe the implementation of a galvanically isolated low-noise power supply board for multi-channel headstage preamplifiers. The implemented galvanically isolated power supply board provides the same quality noise free recording as the battery power supply. The non-isolated part of the power supply board is powered by standard 230 V AC/6 V DC wall mount adapter or USB cable. The described galvanically isolated power supply board can replace the batteries in preamplifier power supplies without any deterioration of the quality of recordings.

Implementation of a miniature sized, battery powered electrophysiological signal-generator for testing multi-channel recording equipments.

Testing electrophysiological recording equipments is an important task in multi-channel extracellular in vivo electrophysiology. In this paper, a miniature, battery powered multi-channel electrophysiological signal-generator (ESG) is described that was designed for this purpose. The device is based on a Xilinx CPLD (Complex Programmable Logic Device) and it is powered by a 3V lithium coin battery. It is a useful tool for calibration and testing the performance, quality and parameters of the recording equipments used for acquiring EEG, field potentials, ECG, EMG, and multiple unit activity. The device is ideally suited to identify instances when errors interfere with the proper recording, and repair of wiring or service of the equipment is needed. Two versions of the device are described; one is for 16 (ESG16), and another is for 32 channels (ESG32). Both versions provide amplitude and time calibration, as well as cross-talk and CMRR (common mode rejection ratio) testing for the recording equipment.

Improved version of the printed circuit board (PCB) modular multi-channel microdrive for extracellular electrophysiological recordings.

The modular multi-channel PCB microdrive was described some years ago, since then several improvements were introduced while using these drives. Utilizing several years of experience with the original PCB microdrive we redesigned it to improve its stability and usability. The application of the printed circuit board technology and the extensive use of flexible fused silica capillaries for fabrication of the microdrive are described in detail. The improved design led to a low cost and light-weight multi-channel microdrive with outstanding modularity for extracellular field, single unit or multiunit tetrode recording up to 64/128 channels.