Edward J. Neafsey

The organization of the rat motor cortex: A microstimulation mapping study

In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rats supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rats frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.

The topographical organization of neurons in the rat medial frontal, insular and olfactory cortex projecting to the solitary nucleus, olfactory bulb, periaqueductal gray and superior colliculus.

In 19 rats two different retrograde tracers (Fast Blue, Diamidino Yellow, Rhodamine-labeled latex microspheres, or wheat germ agglutinin conjugated with HRP) were injected into the solitary nucleus (NTS) and either the olfactory bulb (OB), periaqueductal gray (PAG) or superior colliculus (SC). The pattern of retrogradely labeled neurons in the medial frontal, insular and olfactory cortices was examined to determine the topographical organization of the cell populations projecting to these subcortical targets and the extent to which they overlapped. In the medial frontal cortex (MFC) SC projections originated most dorsally, while NTS and OB projections originated most ventrally and exhibited slight overlap. PAG projections originated from virtually the entire MFC and overlapped with cells projecting to the OB, NTS and SC. These results are consistent with the role of dorsal MFC as the rats frontal eye field and the ventral MFC as a visceral motor area. Laterally, in the insular cortex there was virtually complete overlap between cells projecting to the NTS and PAG. The extensive overlap of PAG projections with NTS projections medially and laterally and with SC projections medially suggests the PAG is involved in a variety of brain visceral and somatic functions. In the piriform cortex there was overlap between cells projecting to the OB and cells projecting to the SC; the cells projecting to the SC were located in the endopiriform nucleus, and may provide a substrate for orienting responses to odors.

A second forelimb motor area exists in rat frontal cortex.

Intracortical microstimulation of 40--50 points in the frontal cortex of ketamine-anesthetized rats using perpendicular penetrations has demonstrated a second forelimb area located rostrally near the frontal pole as well as confirming the existence of a more caudally located forelimb area just anterior to bregma. Cortex where neck and/or vibrissae movements were evoked separated the two forelimb areas. The rostral and caudal forelimb areas defined by microstimulation correspond with patches of corticospinal neurons labeled with HRP following injections of this tracer into the cervical enlargement. Digit movements were commonly evoked from the rostral forelimb area but were rarely elicited from the caudal forelimb area. The question of whether the rostral forelimb region is part of primary or supplementary motor cortex is not yet able to be answered.

The effect of medial frontal cortex lesions on cardiovascular conditioned emotional responses in the rat

The effect of ventral medial frontal cortex (MFC) lesions on heart rate and blood pressure during conditioned emotional responses (CER) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats (n = 11) sustained bilateral lesions of the infralimbic and ventral prelimbic regions of the MFC via microinjection of the neurotoxin N-methyl-D-aspartate; Controls (n = 13) received sterile saline. Following a 2-week recovery period, all animals were trained; one of two tones served as the conditioned stimulus (CS) and a 2 mA footshock served as the unconditioned stimulus (US). The CS+ tone was consistently paired with the US, while the CS- tone was randomly paired with the US. Heart rate and blood pressure were recorded during CS+ and CS- presentations before and after administration of the following pharmacological agents: atropine, atenolol, and atropine + atenolol. All animals responded to the CS+ with increased BP compared to baseline; the increase was not significantly different between groups. Controls responded to the CS+ with increased HR, while MFC-lesioned animals displayed a bimodal HR response which was not significantly different from baseline, but was significantly different from Controls. Pharmacological blockade of the HR response revealed coactivation of the sympathetic and parasympathetic nervous systems during the CS+, with a significant decrease (52%) in the sympathetic tachycardia component of the CS+ HR response in MFC-lesioned rats as compared to Controls; the parasympathetic bradycardia component was not altered by MFC lesions. In all cases, CS- responses were smaller than the CS+ responses. Pharmacological analysis revealed that the CS- HR response was mediated by the sympathetic component only, which was also significantly reduced in MFC-lesioned animals as compared to Controls. This significant reduction in the sympathetically mediated HR component of both the reinforced CER (CS+) and the unreinforced CER (CS-) following ventral MFC lesions implies that the MFC is necessary for complete sympathetic activation of cardiovascular responses to both severely and mildly stressful stimuli. The role of the MFC in emotion is also discussed.

Cardiovascular and respiratory responses to electrical and chemical stimulation of the hippocampus in anesthetized and awake rats

Electrical (30-60-s trains of 0.25-ms pulses at 25 Hz, currents 10-150 microA) and chemical (microinjections of 0.1-0.5 microliters of a 1.0 M glutamate solution) stimulation of the hippocampal formation in the anesthetized and the awake rat evokes marked decreases in heart rate, blood pressure and slower, deeper, more regular respirations. Artificial ventilation (2 ml/breath; 100 breaths/min) has no effect on the cardiovascular responses, indicating that these effects are not secondary to respiratory changes. Administration of methyl atropine (0.4 mg/kg) eliminates the bradycardia response and attenuates or obliterates the blood pressure response but does not alter the respiratory response. This suggests that the cardiovascular responses are mediated partially by the vagus nerve and partially by sympathetic influences. Ablation of the medial frontal cortex, a visceral motor region which projects directly to the nucleus of the solitary tract and which receives a heavy direct projection from the CA1 and subicular cell fields of the ventral hippocampus, markedly attenuates or eliminates the cardiovascular and respiratory responses to stimulation of the ventral but not the dorsal hippocampus. The possibility that the medial frontal cortex may be a relay by which the hippocampus influences cardiovascular responses, including those observed during stress, is discussed.

Phenylethanolamine N-methyltransferase has β-carboline 2N-methyltransferase activity: hypothetical relevance to Parkinson’s disease

Mammalian brain has a beta-carboline 2N-methyltransferase activity that converts beta-carbolines, such as norharman and harman, into 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin 1-methyl-4-phenylpyridinium cation (MPP+). The identity and physiological function of this beta-carboline 2N-methylation activity was previously unknown. We report pharmacological and biochemical evidence that phenylethanolamine N-methyltransferase (EC 2.1.1.28) has beta-carboline 2N-methyltransferase activity. Specifically, purified phenylethanolamine N-methyltransferase (PNMT) catalyzes the 2N-methylation (21.1 pmol/h per unit PNMT) of 9-methylnorharman, but not the 9N-methylation of 2-methylnorharmanium cation. LY134046, a selective inhibitor of phenylethanolamine N-methyltransferase, inhibits (IC50 1.9 microM) the 2N-methylation of 9-methylnorharman, a substrate for beta-carboline 2N-methyltransferase. Substrates of phenylethanolamine N-methyltransferase also inhibit beta-carboline 2N-methyltransferase activity in a concentration-dependent manner. beta-Carboline 2N-methyltransferase activity (43.7pmol/h/mg protein) is present in human adrenal medulla, a tissue with high phenylethanolamine N-methyltransferase activity. We are investigating the potential role of N-methylated beta-carbolinium cations in the pathogenesis of idiopathic Parkinsons disease. Presuming that phenylethanolamine N-methyltransferase activity forms toxic 2N-methylated beta-carbolinium cations, we propose a novel hypothesis regarding Parkinsons disease-a hypothesis that includes a role for phenylethanolamine N-methyltransferase-catalyzed formation of MPP+ -like 2N-methylated beta-carbolinium cations.

Cytoarchitecture of the dorsal thalamus of the rat

Although several neuroanatomical studies have previously described various subdivisions of the rat thalamus, no comprehensive description of the entire thalamus accompanied by photomicrographs has been available. To provide such a description, the cytoarchitecture of the normal rat thalamus was studied in the coronal plane using a series of celloidin embedded, Nissl-stained 33 micrometers sections spaced 400 micrometers apart. Using the criteria of cell packing density, relative cell size, and the presence or absence of fibers, the thalamus can be subdivided into a ventral nuclear complex which includes the ventrolateral, ventromedial, and ventrobasal nuclei; the intralaminar nuclei which include central medial, central lateral, paracentral and parafascicular nuclei; the midline nuclei which include the medioventral, paratenial, rhomboid, paraventricular, and submedial nuclei; the anterior nuclear group which include the anterodorsal, anteroventral, and anteromedial nuclei; the mediodorsal nucleus; the lateral nuclear complex including both lateral posterior and lateral dorsal; the posterior nuclear complex; the reticular nucleus; and the diencephalic-mesencephalic junction. The terminology used is based on previous studies.

A simple method for glass insulating tungsten microelectrodes

A method for insulating tungsten wires with glass by collapsing a glass capillary tube around the wire is described. A common laboratory electrode puller can be used. A new method for removing the glass from the tip using hydrofluoric acid is also described.

Substantia nigra single unit activity during penicillin-induced focal cortical epileptiform discharge in the rat.

In urethane anesthetized rats single unit activity was recorded in the substantia nigra (SN) during focal cortical epileptiform discharges induced by topical application of penicillin to the cortical surface. Eighty percent of SN units responded during the cortical interictal spike discharge, 50% with an initial burst or increase in firing rate and 30% with an initial inhibition or decrease in firing rate. In view of the SNs widespread projections to thalamus and brainstem, these results suggest the SN may be a prominent element of the pathway involved in the spread and generalization of cortical epileptiform activity.

Precentral cortical zones related to flexion and extension in two hindlimb movements in the monkey

Abstract Single units were recorded in the leg region of precentral cortex in two alert rhesus monkeys while each performed two separate leg movements, a pedaling movement involving both legs and an ankle flexion-extension movement by the leg contralateral to the cortex studied. Most units could be classed as +F or +E for each movement, depending on whether they were activated during the flexion (+F) or extension (+E) phase of movement. The electrode penetrations were spaced 1 mm apart in a grid pattern (30–40 tracks/monkey). When the locations of +F or +E units for each movement were plotted on the grid of penetrations, they appeared to be organized into large homogeneous zones of either +F or +E cells with surprisingly little overlap between zones. The zones for the two different movements were similar but not identical. Consistency from one movement to the other improved if the pattern of EMG activity during the two movements was taken into account. These data suggest that relatively complex muscle synergies may be represented in the precentral cortex.